We claim:
1. A method for the preparation of a chiral 4-substituted 2-piperidinone comprising:
(1) reacting a 3-substituted glutaric anhydride of the formula
12
wherein R1 is aryl, alkyl, or any other groups, with a chiral amine of the formula (I)
13
as a chiral auxiliary to obtain a mixture of hemiamides, wherein Ar represents aromatic groups and R represents alkyl groups;
(2) reducing an acid group of the hemiamide to a primary alcohol;
(3) halogenating the primary alcohol to give a halide; and
(4) cyclizing the halide with a base to produce a chiral 2-piperidinone.
2. A method according to claim 1, wherein the chiral amine is chiral primary amines or chiral amino acid derivatives.
3. A method according to claim 1, wherein the aromatic group of the chiral amine is phenyl.
4. A method according to claim 1, wherein the alkyl group of the chiral amine is methyl.
5. A method according to claim 1, wherein the chiral amine is methyl benzylamine.
6. A method according to claim 1, wherein the chiral amine is (S)-methylbenzylamine.
7. A method according to claim 1, wherein R1 is 4FC6H4.
8. A method for the preparation of a chiral trans-3,4-disubstituted 2-piperidinone comprising:
(1) reacting a 3-substituted glutaric anhydride of the formula
14
wherein R1 is aryl, alkyl, or any other groups, with a chiral amine of the formula (I)
15
as a chiral auxiliary to obtain a mixture of hemiamides, wherein Ar represents aromatic groups and R represents alkyl groups;
(2) reducing an acid group of the hemiamide to a primary alcohol;
(3) halogenating the primary alcohol to give a halide;
(4) cyclizing the halide with a base to produce a chiral 2-piperidinone; and
(5) acylating an alpha carbon of the 2-piperidinone to give a chiral trans-3,4-disubstituted 2-piperidinone.
9. A method according to claim 8, wherein the chiral amine is chiral primary amines or chiral amino acid derivatives.
10. A method according to claim 8, wherein the aromatic group of the chiral amine is phenyl.
11. A method according to claim 8, wherein the alkyl group of the chiral amine is methyl.
12. A method according to claim 8, wherein the chiral amine is methyl benzylamine.
13. A method according to claim 8, wherein the chiral amine is (S)-methylbenzylamine.
14. A method according to claim 8, wherein R1 is 4FC6H4.
15. A method for the preparation of a trans-3,4-disubstituted piperidine of the formula of
16
wherein R1 is aryl, alkyl, or any other groups, R2 is alkyl, or any group substituted alkyl, and R3 is hydrogen, alkyl, or any group substituted alkyl, comprising:
(1) reacting a 3-substituted glutaric anhydride of the formula
17
wherein R1 is aryl, alkyl, or any other groups, with a chiral amine of the formula (I)
18
as a chiral auxiliary to obtain a mixture of hemiamides, wherein Ar represents aromatic groups and R represents alkyl groups;
(2) reducing an acid group of the hemiamide to a primary alcohol;
(3) halogenating the primary alcohol to give a halide;
(4) cyclizing the halide with a base to produce a chiral 2-piperidinone;
(5) acylating at the alpha carbon of the 2-piperidinone to give a chiral trans-3,4-disubstituted 2-piperidinone; and
(6) reducing ester and amide groups of the chiral 3,4-disubstituted 2-piperidinone to form a trans-3,4-disubstituted piperidine.
16. A method for the preparation of a chiral paroxetine comprising:
(1) reacting a 3-aryl glutaric anhydride of the formula
19
wherein R1 is aryl, with a chiral amine of the formula (I)
20
as a chiral auxiliary to obtain a mixture of hemiamides, wherein Ar represents aromatic groups and R represents alkyl groups;
(2) reducing an acid group of the hemiamide to a primary alcohol;
(3) halogenating the primary alcohol to give a halide;
(4) cyclizing the halide with a base to produce a chiral 2-piperidinone;
(5) acylating at the alpha carbon of the 2-piperidinone to give a chiral trans-3,4-disubstituted 2-piperidinone;
(6) reducing ester and amide groups of the chiral trans-3,4-disubstituted 2-piperidinone to provide a trans-3,4-disubstituted piperidine; and,
(7) converting a hydroxyl group of trans-3,4-disubstituted piperidine to an aryl ether and then removing the chiral auxiliary by hydrofenolysis to obtain a chiral paroxetine hydrochloride.
17. A method for the preparation of a chiral paroxetine comprising:
(1) reacting a 3-aryl glutaric anhydride of the formula
21
wherein R1 is aryl, with a chiral amine of the formula (I)
22
as a chiral auxiliary to obtain a mixture of hemiamides, wherein Ar represents aromatic groups and R represents alkyl groups;
(2) reducing an acid group of the hemiamide to a primary alcohol;
(3) halogenating the primary alcohol to give a halide;
(4) cyclizing the halide with a base to produce a chiral 2-piperidinone;
(5) acylating at the alpha carbon of the 2-piperidinone to give a chiral trans-3,4-disubstituted 2-piperidinone;
(6) reducing ester and amide groups of the chiral trans-3,4-disubstituted 2-piperidinone to provide a trans-3,4-disubstituted piperidine;
(7) crystallizing the trans-3,4-disubstituted piperidine and converting a hydroxyl group of this compound to a sulfonate followed by a treatment with sesamol and potassium alkoxide to provide a free amine;
(8) converting the free amine to a hydrochloride salt and purifying the hydrochloride salt by recrystallization; and
(9) removing the chiral auxiliary by hydrogenolysis to obtain a chiral paroxetine hydrochloride.
18. (3S)-3 -(4-fluorophenyl)-5-oxo-5-(1S)-( 1-phenylethylamino)pentanoic acid 7a of the following formula
23
wherein R1 represents 4FC6H4 and R2 represents H.
19. (3S)-3-(4-fluorophenyl)-5-oxo-5-(1S)-( 1-phenylethylamino)pentanoic acid 7b of the following formula
24
wherein R1 represents H and R2 represents 4FC6H4.
20. (3R)-3-(4-fluorophenyl)-5-hydroxypentanoic acid (1S)-1-phenylethylamide 8.
21. (3S)-5-bromo-3-(4-fluorophenyl)pentanoic acid (1S)-1-phenylethyl amide 9.
22. (4R)- 4-(4-Fluorophenyl)- 1-(1S)-(1-phenylethyl)piperidin-2-one 10.
23. (3S,4R)-4-(4-Fluorophenyl)-3-methoxycarbonyl- 1-(1S)-(1-phenylethyl)piperidin-2-one 11.
24. (3S,4R)-4-(4-Fluorophenyl)-3-hydroxymethyl- 1-(1S)-( 1-phenylethyl)piperidine 12.
25. A methanesulfonate 13 of the following formula
25
wherein R represents O2SCH3.
26. A free amine 14a of the following formula
26
27. (3S,4R)-3-(Benzo1,3dioxol-5-yloxymethyl)-4-(4-fluorophenyl)- 1-(1S)-(1-phenylethyl)-piperidine hydrochloride salt 14b.
The claims below are in addition to those above.
All refrences to claim(s) which appear below refer to the numbering after this setence.
1. A bicycle seat height adjusting assembly comprising:
an insert tube sized to be slidably receivable within a seat tube of a bicycle type apparatus, said insert tube having an inner wall and an exterior wall, said insert tube further having a lower area and an upper area;
an axially slidable seat post positionable to different heights within said insert tube and adapted to support a bicycle seat at a top portion of said seat post;
means for preventing said seat post from rotating relative to said insert tube;
said seat post being substantially tubular in shape with an open bottom end, said seat post having an upper section and a lower section, said seat post having a seat post inner wall and a seat post outer wall, said seat post having an inner area within said seat post inner walls;
a main spring positioned substantially within said insert tube and extending up into said seat post, said main spring urging said seat post in an upward direction;
a plurality of locking holes formed longitudinally along a first side of said insert tube;
a first longitudinal groove formed along said inner wall of said insert tube, said first longitudinal grove being set in generally corresponding alignment with said plurality of locking holes;
a seat post locking pin and supplemental lock spring substantially positioned within said lower section of said seat post, said locking pin being sized and aligned to engage said locking holes, said locking pin having an outer end portion and an inner end portion, said locking pin having a locking dog portion located substantially at said outer end portion of said locking pin;
a first spline rod with a plurality of wedging projections, said first spline rod with wedging projections containing said first spline rod from which each of said wedging projections protrude, said first spline rod with wedging projections being slidably positioned within said first longitudinal groove, said first spline rod with wedging projections having a total depth substantially equal to the total depth of said first longitudinal groove, each of said wedging projections being positioned in corresponding relation to each of said locking holes;
an actuation lever being operably connected to said first spline rod with wedging projections, wherein pulling of said actuation lever moves each of said wedging projections into each said locking hole, wherein one of said wedging projections pushes said locking pin out of one of said locking holes, wherein said wedging projections are all equally drawn into each corresponding said locking hole, to fully limit said locking pin from entering into any of said locking holes and therefore allow said seat post to rise upwardly;
a return spring means for urging said first spline rod with wedging projections in a return direction, wherein releasing of said actuation lever allows said firstspline rod with wedging projections to be urged in a return direction and cause said wedging projections to substantially withdraw from said locking holes, thereby allowing said supplemental lock spring to urge said locking dog portion back into any one of said locking holes, to thereby set said locking dog portion into a locked position, to thereby relock said seat post at a given height, whereby the height of the seat is adjusted when said first spline rod with wedging projections is moved to thereby push said locking pin out of one of said locking holes and said seat post is placed into a selected position by a cyclist’s buttocks between said locked position;
a maximum height set means, whereby the operator is able to limit said seat post from rising beyond an exact, personally set, optimum height.
2. A bicycle seat height adjusting assembly according to claim 1, wherein each of said wedging projections comprises a generally wedge shape exterior, each of said wedging projections having an outer edge positioned at an outermost section of each of said wedging projections.
3. A bicycle seat height adjusting assembly according to claim 2, wherein each of said wedging projections further comprise an inward curve formed at said outer edge of each said wedging projection, whereby said locking pin is able to slide up and over each said wedging-shaped exterior as said locking pin rises with said seat post.
4. A bicycle seat height adjusting assembly according to claim 1, wherein said locking pin further comprises a supplemental wedge formed adjacent to said locking dog portion of said locking pin, said wedging projections and said first spline rod being positioned substantially within said first longitudinal groove, said supplemental wedge being set in alignment with said wedging projections, open spaces are positioned and sized between each of said wedging projections to allow said supplemental wedge to pass between said wedging projections when said locking dog portion is in said locked position, wherein the cyclist moving said actuation lever causes one of said wedging projections to push back said supplemental wedge and thereby unlock said locking dog portion from said locking holes, whereby release of said actuation lever by the cyclist allows said wedging projections to move away from said locking holes to thereby allow said supplemental wedge to re-enter into one of said open spaces and simultaneously allow said locking dog portion to relock into one of said lock holes.
5. A bicycle seat height adjusting assembly according to claim 4, further comprising a first vertical slot formed substantially through said outer end portion of said locking pin, said first vertical slot formed between said locking dog portion and said supplemental wedge, said first vertical slot being sized and aligned to allow said first spline rod to enter into said first vertical slot and thereby further enable said locking dog portion to enter into one of said locking holes.
6. A bicycle seat height adjusting assembly according to claim 5, further comprising a second spline rod, said wedging projections connecting from said first spline rod to said second spline rod with said open spaces positioned between each of said wedging shapes to allow said supplemental wedge to pass through said open spaces when said locking dog portion is in said locked position, whereby said second spline rod adds strength and support to said first spline rod with wedging projections.
7. A bicycle seat height adjusting assembly according to claim 6, further comprising a second vertical slot and a second locking dog portion that is positioned at said outer end portion of said locking pin, said second vertical slot being formed between said second locking dog portion and said supplemental wedge, said second vertical slot being sized and aligned to allow said second spline rod to enter into said second vertical slot and thereby further enable said first and second locking dog portions to enter into one of said locking holes.
8. A bicycle seat height adjusting assembly according to claim 6, wherein each of said wedging projections are flat and equally thick pieces of material that extend from said first spline rod to said second spline rod, said wedging projections having outer edges.
9. A bicycle seat height adjusting assembly according to claim 8, wherein each of said wedging projections further comprise a taper formed at said outer edges of each said wedging shape whereby said supplemental wedge is able to slide up and over each said wedging projection as said locking pin rises with said seat post.
10. A bicycle seat height adjusting assembly according to claim 6, wherein said supplemental wedge comprises a generally wedge shaped exterior, said supplemental wedge having an outer edge portion.
11. A bicycle seat height adjusting assembly according to claim 10, wherein said supplemental wedge further comprises an inward curve formed at said outer edge portion of said supplemental wedge, whereby said supplemental wedge is able to slide up and over each said wedging projection as said locking pin rises with said seat post.
12. A bicycle seat height adjusting assembly according to claim 5, wherein each of said locking holes are divided into two or more locking holes to thereby accommodate and support said locking dog portion and said supplemental wedge separately.
13. A bicycle seat height adjusting assembly according to claim 1, wherein said main spring comprises a third tubular structure having a substantially open top end and a substantially closed bottom end, said third tubular structure being substantially connected to said lower area of said insert tube, said third tubular structure being substantially similar in length to said insert tube, said third tubular structure thereby extending lengthwise into said seat post inner area of said seat post, said third tubular structure having a substantially open top end, said substantially open top end of said third tubular structure having a perimeter area positioned around the substantially open top end, an air seal positioned around the perimeter area of the substantially open top end of said third tubular structure, wherein pressurized air is not able to pass between said inner walls of said seat post and said air seal to form a first air chamber within said seat post and a second air chamber within said third tubular structure, said substantially open top end of said third tubular structure allowing the flow of said pressurized air between said first air chamber and said second air chamber to thereby create a main air spring with a very even spring rate, urging said seat post upwardly relative to said insert tube; said substantially open top end of said third tubular structure being sized to control the rate of air flow between said first air chamber and said second air chamber to thereby create a dampening effect on the speed at which said seat post is able to rise; an air valve, positioned substantially through the bottom end of said third tubular structure, communicating with said first air chamber and said second air chamber, said air valve containing means for controlling a supply of pressurized air within said first air chamber and said second air chamber.
14. A bicycle seat height adjusting assembly according to claim 13, wherein said main air spring further includes a fourth tubular structure having a closed top end and an open bottom end that is fully and slidably positioned within the seat post inner walls of said seat post, said third tubular structure being slidably and partially positioned within said fourth tubular structure, whereby said main air spring becomes a removable air spring cartridge.
15. A bicycle seat height adjusting assembly according to claim 1, wherein said maximum height set means comprises a second groove formed lengthwise along a second side of said inner wall of said insert tube, said second groove having a top surface, said second groove having second walls that define said second groove, a plurality of threaded post holes being positioned along a second side of said seat post outer wall of said seat post, said plurality of threaded post holes positioned in said lower section of said seat post, said threaded post holes positioned in alignment with said second groove; a maximum height set screw that is sized to be removably receivable within any of said threaded post holes, a portion of said maximum height set screw is positioned within said second groove to limit the upward movement of said seat post upon said maximum height set screw engaging said top surface of said second groove, whereby the operator is able to limit said seat post from rising beyond an exact, personally set, maximum height.
16. A bicycle seat height adjusting assembly according to claim 15, further including an access opening formed through said insert tube, whereby said maximum height set means is accessible to allow for adjustment of said maximum height set means.
17. A bicycle seat height adjusting assembly according to claim 16, wherein said preventing means against rotation of said seat post comprises a seat post boss that is positioned on said seat post outer wall, said seat post boss being further positioned in said lower section of said seat post, said seat post boss is positioned in alignment with said second groove and extends into said second groove, whereby said seat post boss is prevented against rotation by said second walls that define said second groove.
18. A bicycle seat height adjusting assembly according to claim 17, wherein said seat post boss includes a ball bearing sized to be wider then said second groove, said ball bearing thereby rolling partially within said second groove, said ball bearing being pressed against said second groove by a supplemental bearing spring, and thereby further preventing said seat post from rotating relative to said insert tube.
19. A bicycle seat height adjusting assembly according to claim 1, wherein said preventing means against rotation for said seat post comprises a third groove that is formed lengthwise along said inner wall of said insert tube, a second boss is positioned on said seat post outer wall, said second seat post boss being further positioned in said lower section of said seat post and is positioned in alignment with said third groove, said second boss extending into said third groove, whereby said seat post boss is further prevented against rotation by said third groove.
20. A bicycle seat height adjusting assembly according to claim 19, wherein said second seat post boss comprises a second ball bearing sized to be wider then said third groove, said second ball bearing being pressed against said third groove by a second supplemental bearing spring, said second ball bearing thereby rolling partially within said third groove, to thereby further prevent said seat post from rotating relative to said insert tube.
21. A bicycle seat height adjusting assembly according to claim 1, wherein said maximum height set means comprises the insert tube being positioned at a given height within said seat tube of the bicycle frame, to thereby set said seat at a rider’s preferred maximum height.
22. A bicycle seat height adjusting assembly according to claim 1, wherein said first spline rod with wedging projections is oriented to be pulled in a downward direction to thereby push said locking pin out of said locking holes.
23. A bicycle seat height adjusting assembly according to claim 1, wherein said first spline rod with wedging projections is oriented to be pulled in an upward direction to thereby push said locking pin out of said locking holes.
24. A bicycle seat height adjusting assembly according to claim 1, wherein said actuation lever is generally connected by a cable with an outer housing or a hydraulic type connective line to said first spline rod with wedging projections, said actuation lever being positionable on the handlebars of said bicycle type apparatus.
25. A bicycle seat height adjusting assembly according to claim 24, wherein said cable or hydraulic type connective line is attached to said first spline rod through said upper area of said insert tube.
26. A bicycle seat height adjusting assembly according to claim 24, wherein said cable or hydraulic type connective element is attached to said first spline rod through an opening in the bicycle frame that extends into the lower area of said insert tube.
27. A bicycle seat height adjusting assembly according to claim 1, wherein said locking pin is slidably contained within a linearly aligned housing.
28. A bicycle seat height adjusting assembly according to claim 1, wherein said locking pin is contained within a pivoting support structure.
29. A bicycle seat height adjusting assembly according to claim 1, further containing a wiper seal positioned at said upper area of said insert tube, said wiper seal being further positioned around said seat post, whereby said wiper seal wipes off dirt from said seat post as said seat post is lowered.
30. A bicycle seat height adjusting assembly according to claim 1, further containing an outer collar section formed substantially around said upper area of said insert tube to limit the amount said insert sleeve will lower into said bicycle seat tube.
31. A bicycle seat height adjusting assembly according to claim 1, wherein said locking pin contains a square profile, said outer end portion of said locking pin further being formed as a curve, whereby said locking pin is able to be fully pushed out of said locking holes while said seat post and said insert tube have a substantially circular configuration.
32. A bicycle seat height adjusting assembly according to claim 1, wherein said main spring contains a compression spring.