1. A process for the preparation of a compound of formula (I)
or salts thereof, comprising catalytic asymmetric hydrogenation of a compound of formula (II)
or salts thereof, in the presence of a catalyst comprising ruthenium and a chiral diphosphine ligand or comprising rhodium and a chiral diphosphine ligand, to yield said compound of formula (I),
wherein
R1 is aryl or heteroaryl,
R2 is lower-alkyl,
R3 is lower-alkyl.
2. The process of claim 1, wherein the the chiral diphosphine ligand is selected from formula (III), (IV), (V), (VI) or (VII)
wherein
R4 is lower-alkyl;
R5 is lower-alkyl;
R6 independently is aryl, heteroaryl, cylcoalkyl or lower-alkyl;
R7 is N(lower-alkyl)2 or piperidinyl;
R8 is lower-alkyl, lower-alkoxy, hydroxy or lower-alkyl-C(O)O\u2014;
R9 and R10 independently are hydrogen, lower-alkyl, lower-alkoxy or di(lower-alkyl)amino; or
R8 and R9 or R9 and R10 which are attached to the same phenyl group, or both R8 attached to different phenyl groups, taken together, are \u2014X\u2014(CH2)n\u2014Y\u2014, wherein X is \u2014O\u2014 or \u2014C(O)O\u2014, Y is \u2014O\u2014 or \u2014N(lower-alkyl)- and n is an integer from 1 to 6; or
R8 and R9, or R9 and R10, together with the carbon atoms to which they are attached, form a naphthyl, tetrahydronaphthyl or dibenzofuran ring;
R11 independently is phenyl or napthyl, substituted with 0 to 7 substituents independently selected from the group consisting of lower-alkyl, lower-alkoxy, di(lower-alkyl)amino, morpholino, phenyl and tri(lower-alkyl)silyl;
R12 independently is lower-alkyl with the proviso that when R11 is phenyl then it is substituted by 0 to 5 substituents.
3. The process of claim 2, wherein the catalyst is of the formula Ru(chiral diphosphine)B2, wherein the chiral diphosphine is characterised by formula (VI) or (VII) as defined in claim 2 and wherein B is CH3COO\u2212, CF3COO\u2212 or a halogenide.
4. The process of claim 3, wherein the chiral diphosphine is selected from the group consisting of (S)-MeOBIPHEP, (S)-BIPHEMP, (S)-TMBTP, (S)-(2-Naphthyl)-MeOBIPHEP, (S)-(6-MeO-2-Naphthyl)-MeOBIPHEP, (S)-TriMeOBIPHEP, (R,R,S,S)-Mandyphos, (S)-BnOBIPHEP, (S)-BenzoylBIPHEP, (S)-pTol-BIPHEMP, (S)-tButylCOOBIPHEP, (S)-iPrOBIPHEP, (S)-pPhenyl-MeOBIPHEP, (S)-pAn-MeOBIPHEP, pTol-MeOBIPHEP, (S)-3,5-Xyl-MeOBIPHEP, (S)-3,5-Xyl-BIPHEMP, (S)-BINAP and (S)-2-Furyl-MeOBIPHEP.
5. The process of claim 4, wherein the chiral diphosphine is (S)-TMBTP, (S)-(2-Naphthyl)-MeOBIPHEP or (S)-(6-MeO-2-Naphthyl)-MeOBIPHEP.
6. The process of claim 3, wherein B is CH3COO\u2212 or CF3COO\u2212.
7. The process of claim 6, wherein the catalyst is selected from the group consisting of Ru(CH3COO\u2212)2((S)-TMBTP), Ru(CF3COO\u2212)2((S)-TMBTP), Ru(CH3COO\u2212)2((S)-(2-Naphthyl)-MeOBIPHEP), Ru(CF3COO\u2212)2((S)-(2-Naphthyl)-MeOBIPHEP), Ru(CH3COO\u2212)2((S)-(6-MeO-2-Naphthyl)-MeOBIPHEP) and Ru(CF3COO\u2212)2((S)-(6-MeO-2-Naphthyl)-MeOBIPHEP).
8. The process of claim 7, wherein the catalytic hydrogenation is carried out at a pressure of 20 to 40 bar.
9. The process of claim 8, wherein the catalytic hydrogenation is carried out at a temperature of 20 to 60\xb0 C.
10. The process of claim 9, wherein the catalytic hydrogenation is carried out in the presence of a base.
11. The process of claim 10, wherein the catalytic hydrogenation is carried out in a solvent which is selected from methanol, dichloromethan, ethanol, tetrahydrofuran, ethylacetat or toluene, or a combination thereof.
12. The process of claim 11, wherein the catalytic hydrogenation is carried out in a solvent which is a 3:2 mixture of methanol and dichloromethan.
13. The process of claim 12, comprising crystallisation of the compound of formula (I).
14. The process of claim 13, comprising crystallisation of the compound of formula (I) as a salt with a primary amine.
15. The process of claim 14, wherein the primary amine is (S)-phenylethylamine.
16. The process of claim 15, wherein the compound of formula (I) is(S)-2-methoxy-3-{4-2-(5-methyl-2-phenyl-oxazol-4-yl)-ethoxy-benzobthiophen-7-yl}-propionic acid.
17. The process of claim 16, comprising the conversion of the compound of formula (I) into a pharmaceutically acceptable salt
18. The process of claim 15, wherein R1 is phenyl.
19. The process of claim 18, wherein R2 is methyl.
20. The process of claim 19, wherein R3 is methyl.
21. A process for the preparation of (S)-2-methoxy-3-{4-2-(5-methyl-2-phenyl-oxazol-4-yl)-ethoxy-benzobthiophen-7-yl}-propionic acid, comprising
a) reacting 4-2-(5-methyl-2-phenyl-oxazol-4-yl)-ethoxy-benzobthiophen-7-carbaldehyde with methoxyacetic acid methyl ester to yield 3-hydroxy-2-methoxy-3-{4-2-(5-methyl-2-phenyl-oxazol-4-yl)-ethoxy-benzobthiophen-7-yl}-propionic acid methyl ester;
b) converting 3-hydroxy-2-methoxy-3-{4-2-(5-methyl-2-phenyl-oxazol-4-yl)-ethoxy-benzobthiophen-7-yl}-propionic acid to (Z)-2-methoxy-3-{4-2-(5-methyl-2-phenyl-oxazol-4-yl)-ethoxy-benzobthiophen-7-yl}-acrylic acid methyl ester;
c) converting (Z)-2-methoxy-3-{4-2-(5-methyl-2-phenyl-oxazol-4-yl)-ethoxy-benzobthiophen-7-yl}-acrylic acid methyl ester to (Z)-2-methoxy-3-{4-2-(5-methyl-2-phenyl-oxazol-4-yl)-ethoxy-benzobthiophen-7-yl}-acrylic acid; and
d) hydrogenating (Z)-2-methoxy-3-{4-2-(5-methyl-2-phenyl-oxazol-4-yl)-ethoxy-benzobthiophen-7-yl}-acrylic acid using a procedure as defined in claim 1 to yield (S)-2-methoxy-3-{4-2-(5-methyl-2-phenyl-oxazol-4-yl)-ethoxy-benzobthiophen-7-yl}-propionic acid.
22. The compound: (Z)-2-methoxy-3-{4-2-(5-methyl-2-phenyl-oxazol-4-yl)-ethoxy-benzobthiophen-7-yl}-acrylic acid methyl ester
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 battery, comprising:
a housing;
an anode within the housing;
an electrolyte within the housing; and
a cathode within the housing, the cathode including a cathode active material comprising less than about 40 percent by weight CuxMyOzXt, wherein M is a metal, X includes one or more halides andor nitrate, x+y is from about 6.8 to about 7.2, and z and t are selected so that the copper in CuxMyOzXt has a formal oxidation state of +2 or greater.
2. The battery of claim 1, wherein M is indium, gallium, arsenic, scandium, yttrium, bismuth, niobium, calcium, or a lanthanide.
3. The battery of claim 1, wherein M is indium.
4. The battery of claim 1, wherein X is chlorine.
5. The battery of claim 1, wherein CuxMyOzXt is CuxInyOzClt.
6. The battery of claim 1, wherein CuxMyOzXt is Cu6InO8Cl.
7. The battery of claim 1, wherein the cathode active material comprises less than about 35 percent by weight CuxMyOzXt.
8. The battery of claim 1, wherein the cathode active material comprises less than about 30 percent by weight CuxMyOzXt.
9. The battery of claim 1, wherein the cathode active material comprises less than about 25 percent by weight CuxMyOzXt.
10. The battery of claim 1, wherein the cathode active material comprises less than about 20 percent by weight CuxMyOzXt.
11. The battery of claim 1, wherein the cathode active material comprises less than about 15 percent by weight CuxMyOzXt.
12. The battery of claim 1, wherein the cathode active material comprises less than about ten percent by weight CuxMyOzXt.
13. The battery of claim 1, wherein the cathode active material comprises less than about five percent by weight CuxMyOzXt.
14. The battery of claim 1, wherein the cathode active material comprises less than about two percent by weight CuxMyOzXt.
15. The battery of claim 1, wherein the cathode active material comprises less than about one percent by weight CuxMyOzXt.
16. The battery of claim 1, wherein x+y is about 6.8.
17. The battery of claim 1, wherein x+y is about 7.2.
18. The battery of claim 1, wherein the copper in CuxMyOzXt has a formal oxidation state of +2.w and +2.w is from +2.0 to +2.4.
19. The battery of claim 1, wherein the copper in CuxMyOzXt has a formal oxidation state of +2.w and +2.w is from +2.2 to +2.4.
20. The battery of claim 1, wherein the cathode comprises less than about ten percent by weight graphite.
21. The battery of claim 1, wherein the cathode comprises less than about five percent by weight graphite.
22. The battery of claim 1, wherein the cathode comprises less than about two percent by weight carbon fibers.
23. The battery of claim 1, wherein the cathode comprises less than about 0.5 percent by weight carbon fibers.
24. The battery of claim 1, wherein the cathode active material further comprises a copper oxide, manganese dioxide, or nickel oxyhydroxide.
25. The battery of claim 1, wherein the cathode active material further comprises a copper oxide.
26. The battery of claim 25, wherein the copper oxide comprises CuO or Cu2O.
27. The battery of claim 1, wherein the cathode active material comprises less than about 20 percent by weight CuxMyOzXt and more than about 80 percent by weight of a copper oxide, manganese dioxide, or nickel oxyhydroxide.
28. The battery of claim 1, wherein the cathode active material comprises less than about 20 percent by weight CuxMyOzXt and more than about 80 percent by weight of a copper oxide.
29. The battery of claim 1, wherein the cathode has a Coulombic capacity of more than about 260 mAhgram.
30. The battery of claim 1, wherein the cathode has a Coulombic capacity of more than about 450 mAhgram.
31. The battery of claim 1, wherein the cathode active material has a resistivity of less than about one Ohm-cm.
32. The battery of claim 1, wherein the cathode active material has a resistivity of less than about 10\u22122 Ohm-cm.
33. The battery of claim 1, wherein the battery has an open circuit voltage of more than about 1.2 Volts.
34. The battery of claim 1, wherein the battery has a open circuit voltage of more than about 1.5 Volts.
35. The battery of claim 1, wherein the battery has a closed circuit voltage of more than about 1.4 Volts on a load of one mAgram of cathode active material.
36. The battery of claim 1, wherein the battery has a closed circuit voltage of more than about one Volt on a load of ten mAgram of cathode active material.
37. The battery of claim 1, wherein the anode comprises zinc.
38. The battery of claim 1, wherein the electrolyte is an alkaline electrolyte.
39. A battery, comprising:
a housing;
an anode within the housing;
a cathode within the housing, the cathode including a first cathode active material and a second cathode active material comprising CuxMyOzXt, wherein M is a metal, X includes one or more halides andor nitrate, x+y is from about 6.8 to about 7.2, and z and t are selected so that the copper in CuxMyOzXt has a formal oxidation state of +2 or greater;
and an alkaline electrolyte,
wherein the battery is a primary battery.
40. The battery of claim 39, wherein the first cathode active material is CuO, MnO2, or NiOOH.
41. The battery of claim 39, wherein the anode comprises zinc.
42. The battery of claim 39, wherein CuxMyOzXt is CuxMyOzClt.
43. The battery of claim 39, wherein CuxMyOzXt is Cu6InO8Cl.
44. A battery, comprising:
a housing;
an anode within the housing;
an alkaline electrolyte within the housing; and
a cathode within the housing, the cathode including a cathode active material comprising CuxMyOzXt, wherein M is a metal, X includes one or more halides andor nitrate, x+y is from about 6.8 to about 7.2, and z and t are selected so that the copper in CuxMyOzXt has a formal oxidation state of +2 or greater,
wherein the battery is a closed system.
45. The battery of claim 44, wherein M is indium, gallium, arsenic, scandium, yttrium, bismuth, niobium, calcium, or a lanthanide.
46. The battery of claim 44, wherein M is indium.
47. The battery of claim 44, wherein X is chlorine.
48. The battery of claim 44, wherein CuxMyOzXt is CuxInyOzClt.
49. The battery of claim 44, wherein CuxMyOzXt is Cu6InO8Cl.
50. The battery of claim 44, wherein the cathode active material comprises more than about 70 percent by weight CuxMyOzXt.
51. The battery of claim 44, wherein the cathode active material comprises more than about 80 percent by weight CuxMyOzXt.
52. The battery of claim 44, wherein the cathode active material comprises more than about 90 percent by weight CuxMyOzXt.
53. The battery of claim 44, wherein the cathode active material comprises more than about 95 percent by weight CuxMyOzXt.
54. The battery of claim 44, wherein the cathode active material comprises more than about 99 percent by weight CuxMyOzXt.
55. The battery of claim 44, wherein x+y is about 6.8.
56. The battery of claim 44, wherein x+y is about 7.2.
57. The battery of claim 44, wherein the copper in CuxMyOzXt has a formal oxidation state of +2.w and +2.w is from +2.0 to +2.4.
58. The battery of claim 44, wherein the copper in CuxMyOzXt has a formal oxidation state of +2.w and +2.w is from +2.2 to +2.4.
59. The battery of claim 44, wherein the battery has an open circuit voltage of more than about 1.2 Volts.
60. The battery of claim 44, wherein the battery has an open circuit voltage of more than about 1.5 Volts.
61. The battery of claim 44, wherein the battery has a closed circuit voltage of more than about 1.4 Volts on a load of one mAgram of cathode active material.
62. The battery of claim 44, wherein the battery has a closed circuit voltage of more than about one Volt on a load of ten mAgram of cathode active material.
63. The battery of claim 44, wherein the anode comprises zinc.
64. A cathode including a cathode active material comprising less than about 40 percent by weight CuxMyOzXt, wherein M is a metal, X includes one or more halides andor nitrate, x+y is from about 6.8 to about 7.2, and z and t are selected so that the copper in CuxMyOzXt has a formal oxidation state of +2 or greater.
65. The cathode of claim 64, wherein M is indium, gallium, arsenic, scandium, yttrium, bismuth, niobium, calcium, or a lanthanide.
66. The cathode of claim 64, wherein M is indium.
67. The cathode of claim 64, wherein X is chlorine.
68. The cathode of claim 64, wherein CuxMyOzXt is CuxInyOzClt.
69. The cathode of claim 64, wherein CuxMyOzXt is Cu6InO8Cl.
70. The cathode of claim 64, wherein the cathode active material comprises less than about 35 percent by weight CuxMyOzXt.
71. The cathode of claim 64, wherein the cathode active material comprises less than about 30 percent by weight CuxMyOzXt.
72. The cathode of claim 64, wherein the cathode active material comprises less than about 25 percent by weight CuxMyOzXt.
73. The cathode of claim 64, wherein the cathode active material comprises less than about 20 percent by weight CuxMyOzXt.
74. The cathode of claim 64, wherein the cathode active material comprises less than about 15 percent by weight CuxMyOzXt.
75. The cathode of claim 64, wherein the cathode active material comprises less than about ten percent by weight CuxMyOzXt.
76. The cathode of claim 64, wherein the cathode active material comprises less than about five percent by weight CuxMyOzXt.
77. The cathode of claim 64, wherein the cathode active material comprises less than about two percent by weight CuxMyOzXt.
78. The cathode of claim 64, wherein x+y is about 6.8.
79. The cathode of claim 64, wherein x+y is about 7.2.
80. The cathode of claim 64, wherein the copper in CuxMyOzXt has a formal oxidation state of +2.w and +2.w is from +2.0 to +2.4.
81. The cathode of claim 64, wherein the copper in CuxMyOzXt has a formal oxidation state of +2.w and +2.w is from +2.2 to +2.4.