1. An adjustable furniture joint comprising:
a vertically disposed support having a longitudinally extending channel and opposing jaws defining an opening to said channel, said jaws having forward surfaces,
a horizontal bracket having one or more rear surfaces in abutting engagement with said forward surfaces,
a key cam having a neck, a head extending from said neck, and a longitudinal dimension, said head having a cross-sectional profile having two laterally extending ears, each ear having an inner surface inclined at an acute angle relative to said longitudinal dimension, said head slidingly received in said channel, said jaws having out-turned surfaces generally in parallel alignment and in abutting engagement with said inner surfaces of said ears, and
means for biasing said head towards said bracket, application of said biasing force causing said inner surfaces of said ears to impinge on said out-turned surfaces of said jaws and urging said jaws inwardly towards said neck.
2. The adjustable furniture joint of claim 1 further comprising:
a clevis having two spaced apart arms, each arm having an aperture,
said means for biasing including said bracket having a rearwardly opening pocket, said key cam having a tab extending from said neck opposite said head, said tab having an opening, said tab interposed between said arms,
a pin received in said opening of said tab and said apertures of said arms, said key cam in pivoting engagement with said clevis about said pin, and
said clevis, tab and pin received in said pocket.
3. The adjustable furniture joint of claim 2 further comprising:
said pocket having a forward wall having a hole,
a threaded fastener received in said hole, and
said clevis having a threaded aperture, said threaded fastener threadedly received in said threaded aperture, tightening of said fastener urging said clevis, pin, and key cam towards said bracket.
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 process for preparing gemcitabine, comprising:
a) reacting lactol intermediate 12A with p-toluenesulfonyl chloride in the presence of a base to obtain a sulfonate intermediate of the formula 13A;
b) coupling the compound of formula 13A with N,O-bis-(trimethylsilyl)-cytosine using a catalyst in an organic solvent to obtain a mixture of \u03b1 and \u03b2 anomers of the 3\u2032,5\u2032-diprotected-N trimethylsilyl-2\u2032-deoxy-2\u2032,2\u2032-difluorocytidine 17;
c) removing the trimethylsylil group and selectively precipitating the \u03b2 isomer of the 3\u2032,5\u2032-diprotected-2\u2032-deoxy-2\u2032,2\u2032-difluorocytidine; and
d) removing the protecting groups to obtain gemcitabine;
2. The process of claim 1 further comprises:
a) optionally converting the gemcitabine into a salt; and
b) optionally purifying the gemcitabine salt by crystallization.
3. A process for preparing gemcitabine or a salt thereof, the process comprising selectively precipitating the \u03b2-anomer of a 3\u2032,5\u2032-di-O-protected-2\u2032-deoxy-2\u2032,2\u2032-difluorocytidine, removing the protecting groups to produce gemcitabine, and, optionally, converting the gemcitabine into a salt.
4. The process of claim 3, wherein the coupling reaction is carried out in an organic solvent selected from acetonitrile, ethyl acetate, n-butyl acetate, chloroform, 1,2-dichloroethane, toluene, one or more xylenes, or a mixture thereof.
5. The process of claim 4, wherein the solvent is 1,2-dichloroethane.
6. The process of claim 1, wherein the coupling reaction is carried out in the presence of a catalyst.
7. The process of claim 1, wherein the 3\u2032,5\u2032-protecting groups are removed by basic hydrolysis.
8. A compound of the formula 13A
wherein R and R\u2032 are the same or different and at least one of R and R\u2032 is phenyl, 2-phenylethenyl (thus forming a cinnamoyl ester), 1-naphthyl, 1-naphthylmethyl, 2-methylbenzyl, 2-methylbenzyl or 4-methylbenzyl.
9. A process for separating the \u03b2-anomer from an anomeric mixture of a 3\u2032,5\u2032-di-O -protected-2\u2032-deoxy-2\u2032,2\u2032-difluorocytidine, the process comprising:
a) dissolving a crude anomeric mixture of a 3\u2032,5\u2032-di-O-protected-N4-trimethylsilyl-2\u2032-deoxy-2\u2032,2\u2032-difluorocytidine in an organic solvent and extracting with water;
b) adding an aqueous solution containing a base to the organic phase to produce a precipitate that is at least enriched in the \u03b2-anomer;
c) collecting the precipitate; and
d) optionally washing the precipitate with an organic solvent and drying.
10. The process of claim 9, wherein the 3\u2032,5\u2032-diprotected-2\u2032-deoxy-2\u2032,2\u2032-difluorocytidine is 3 \u2032,5\u2032-dicinnamoyl-2\u2032-deoxy-2\u2032,2\u2032-difluorocytidine, 3\u2032,5\u2032-dinaphthoyl-2\u2032-deoxy-2\u2032,2\u2032-difluorocytidine, 3\u2032,5\u2032-dinaphthylmethyl-2\u2032-deoxy-2\u2032,2\u2032-difluorocytidine, 3\u2032,5\u2032-di-2-methylbenzyl -deoxy-2\u2032,2\u2032-difluorocytidine, or 3\u2032,5\u2032-di-4-methylbenzyl-2\u2032-deoxy-2\u2032,2\u2032-difluorocytidine.
11. The process of claim 10, wherein the 3\u2032,5\u2032-diprotected-2\u2032-deoxy-2\u2032,2\u2032-difluorocytidine is 3\u2032,5\u2032-dicinnamoyl-2\u2032-deoxy-2\u2032,2\u2032-difluorocytidine.
12. The process of claim 9, wherein the solvent for precipitating the 3\u2032,5\u2032-diprotected-2\u2032-deoxy-2\u2032,2\u2032-difluorocytidine is selected from dichloromethane, chloroform, ethyl acetate, 1-propyl acetate, 2-propyl acetate, butyl acetate, tert-butyl acetate, o-xylene, m-xylene, o-dichlorobenzene, toluene, and mixtures thereof.
13. The process of claim 12, wherein the solvent for precipitating the 3\u2032,5\u2032-di-O-protected-2\u2032-deoxy-2\u2032,2\u2032-difluorocytidine is ethyl acetate.
14. The process of claim 9, further comprising removing the protecting groups of the \u03b2-anomer-enriched 3\u2032,5\u2032-di-O-protected-2\u2032-deoxy-2\u2032,2\u2032-difluorocytidine to produce gemcitabine, and, optionally converting the gemcitabine into a salt.
15. A process for enriching the content of the \u03b2-anomer from an anomeric mixture of a 3\u2032,5\u2032-di-O-protected-2\u2032-deoxy-2\u2032,2\u2032-difluorocytidine, the process comprising:
a) slurrying the anomeric mixture of the 3\u2032,5\u2032-di-O-protected-2\u2032-deoxy-2\u2032,2\u2032-difluorocytidine in an organic solvent;
b) isolating the solid from the slurry;
c) optionally washing the solid with an organic solvent; and
d) optionally drying the solid.
16. The process of claim 15, wherein the 3\u2032,5\u2032-di-O-protected-2\u2032-deoxy-2\u2032,2\u2032-difluorocytidine is 3\u2032,5\u2032-dicinnamoyl-2\u2032-deoxy-2\u2032,2\u2032-difluorocytidine, 3\u2032,5\u2032-dinaphthoyl-2\u2032-deoxy-2\u2032,2\u2032-difluorocytidine, 3\u2032,5\u2032-dinaphthylmethyl-2\u2032-deoxy-2\u2032,2\u2032-difluorocytidine, 3\u2032,5\u2032-di-2-methylbenzyl-2\u2032-deoxy-2\u2032,2\u2032-difluorocytidine, or 3\u2032,5\u2032-di-4-methylbenzyl-2\u2032-deoxy-2\u2032,2\u2032-difluorocytidine.
17. The process of claim 16, wherein the 3\u2032,5\u2032-di-O-protected-2\u2032-deoxy-2\u2032,2\u2032-difluorocytidine is 3\u2032,5\u2032-dicinnamoyl-2\u2032-deoxy-2\u2032,2\u2032-difluorocytidine.
18. The process of claim 17, wherein the solvent used for slurrying the anomeric mixture of the 3\u2032,5\u2032-dicinnamoyl-2\u2032-deoxy-2\u2032,2\u2032-difluorocytidine is dichloromethane, ethyl acetate, methanol, 2-propanol, acetone, acetonitrile, or a mixture thereof.
19. The process of claim 17, wherein the ratio between 3\u2032,5\u2032-dicinnamoyl-2\u2032-deoxy-2\u2032,2\u2032-difluorocytidine and the solvent in the slurrying process is at least about 1:1 (gml).
20. The process of claim 19, wherein the ratio between 3\u2032,5\u2032-dicinnamoyl-2\u2032-deoxy-2\u2032,2\u2032-difluorocytidine and the solvent in the slurrying process is at least about 1:10 (gml).
21. The process of claim 3, wherein the gemcitabine or salt thereof is obtained in a purity of at least about 98%.
22. The process of claim 21, wherein the gemcitabine or salt thereof is obtained in a purity of at least about 99.5%.
23. The process of claim 22, wherein the gemcitabine or salt thereof is obtained in a purity of at least about 99.9%.