US4876364A
Expired / Lapsed
US
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Hydrogenation process for the formation of 4A,5-dihydro HMG-CoA reductase inhibitors
Assignee: Merck and Co Inc
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Filing: 1987-09-03
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Granted: 1989-10-24
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Expires: 2007-09-03
Abstract
Abstract A novel hydrogenation process, employing an iridium or rhodium catalyst, in an alcoholic solvent mixture, for the reduction of the 4a,5 double bond in the polyhydronaphthyl ring of des-( alpha -methylbutyryl)-8-hydroxy-lovastatin or analogs thereof, is disclosed.
Inventors
- 👤 Ann D. Schuda
- 👤 Thomas R. Verhoeven
- 👤 Ichiro Shinkai
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-10-23 13:32
CPC Classifications
C; C07; C07D; C07D309/00; C07D309/16; C07D309/28; C07D309/30; C07F; C07F7/00; C07F7/02; C07F7/08; C07F7/18; C07F7/1804
Claims Analysis
Total Claims: 19
Claim 1
Independent Claim
168 words
A process for the preparation of a compound of structural formula (III): ##STR3## wherein: X is OH, NH 2 or OR; where R is C 1-5 alkyl, C 3-7 cycloalkyl, phenylC 1-3 alkyl, or substituted phenylC 1-3 alkyl in which the substituent is halogen, CN, or CF 3 ; R 1 is H or CH 3 or CH 2 OSi(Me) 2 t--C 4 H 9 or OSi(Me) 2 t--C 4 H 9 ; R 2 is H or CH 2 OSi(Me) 2 t--C 4 H 9 or OSi(Me) 2 t--C 4 H 9 ; provided that when R 1 or R 2 is CH 2 OSi(Me) 2 t--C 4 H 9 the other is H; and one and only one of R 1 and R 2 can be OSi(Me) 2 t--C 4 H 9 ; and b is a double bond or a single bond; which comprises: contacting a compound of structural formula (II) ##STR4## with 1,5-cyclooctadiene(pyridine)(tricyclohexyl-phosphine)iridium(I)hexafluorophosphate or norbornadiene-1,4-bis(diphenylphosphino)butane rhodium(I)hexafluoroborate; in an alcoholic solvent, under hydrogen gas pressure.
Claim 2
Dependent Claim
168 words
A process for the preparation of a compound of structural formula (III): ##STR3## wherein: X is OH, NH 2 or OR; where R is C 1-5 alkyl, C 3-7 cycloalkyl, phenylC 1-3 alkyl, or substituted phenylC 1-3 alkyl in which the substituent is halogen, CN, or CF 3 ; R 1 is H or CH 3 or CH 2 OSi(Me) 2 t--C 4 H 9 or OSi(Me) 2 t--C 4 H 9 ; R 2 is H or CH 2 OSi(Me) 2 t--C 4 H 9 or OSi(Me) 2 t--C 4 H 9 ; provided that when R 1 or R 2 is CH 2 OSi(Me) 2 t--C 4 H 9 the other is H; and one and only one of R 1 and R 2 can be OSi(Me) 2 t--C 4 H 9 ; and b is a double bond or a single bond; which comprises: contacting a compound of structural formula (II) ##STR4## with 1,5-cyclooctadiene(pyridine)(tricyclohexyl-phosphine)iridium(I)hexafluorophosphate or norbornadiene-1,4-bis(diphenylphosphino)butane rhodium(I)hexafluoroborate; in an alcoholic solvent, under hydrogen gas pressure.
Claim 3
Dependent Claim
10 words
A process of claim 1 wherein the catalyst is 1,5-cyclooctadiene(pyridine)(tricyclohexylphosphine)iridium(I)hexafluorophosphate.
Claim 4
Dependent Claim
22 words
A process of claim 2 wherein the alcoholic solvent is a mixture of dichloromethane, or chloroform, or chlorobenzene and ethanol or isopropanol.
Claim 5
Dependent Claim
16 words
A process of claim 3 wherein the alcoholic solvent is a mixture of dichloromethane and isopropanol.
Claim 6
Dependent Claim
59 words
A process of claim 1 wherein R 1 is H, or CH 3 , or CH 2 OSi(Me) 2 t--C 4 H 9 ; R 2 is H or CH 2 OSi(Me) 2 t--C 4 H 9 ; provided that when R 1 or R 2 is CH 2 OSi(Me) 2 t--C 4 H 9 the other is H.
Claim 7
Dependent Claim
15 words
A process of claim 1 wherein: X is OH and b is a double bond.
Claim 8
Dependent Claim
108 words
A process of claim 6 wherein the compound (III) prepared is selected from the group wherein a. R 1 is CH 3 , R 2 is H, b. R 1 is CH 2 OSi(Me) 2 t--C 4 H 9 , R 2 is H, c. R 1 is H, R 2 is CH 2 OSi(Me) 2 t--C 4 H 9 , d. R 1 is OSi(Me) 2 t--C 4 H 9 , R 2 is H, e. R 1 is H, R 2 is OSi(Me) 2 t--C 4 H 9 , f. R 1 is CH 3 , R 2 is OSi(Me) 2 t--C 4 H 9 .
Claim 9
Dependent Claim
16 words
A process of claim 1 wherein X is NH 2 and b is a double bond.
Claim 10
Dependent Claim
60 words
A process of claim 8 wherein the compound (III) prepared is selected from the group wherein: a. R.sub.1 =CH.sub.3, R.sub.2 =H; b. R.sub.1 =CH.sub.2 OSi(Me).sub.2 t--C.sub.4 H.sub.9, R.sub.2 =H; c. R.sub.1 =H, R.sub.2 =CH.sub.2 OSi(Me).sub.2 t--C.sub.4 H.sub.9 ; d. R.sub.1 =OSi(Me).sub.2 t--C.sub.4 H.sub.9, R.sub.2 =H; e. R.sub.1 =H, R.sub.2 =OSi(Me).sub.2 t--C.sub.4 H.sub.9 ; f. R.sub.1 =CH.sub.3, R.sub.2 =OSi(Me).sub.2 t--C.sub.4 H.sub.9.
Claim 11
Dependent Claim
15 words
A process of claim 1 wherein X is OR and b is a double bond.
Claim 12
Dependent Claim
11 words
A process of claim 10 wherein X is OCH 3 .
Claim 13
Dependent Claim
60 words
A process of claim 11 wherein the compound (III) prepared is selected from the group wherein: a. R.sub.1 =CH.sub.3, R.sub.2 =H; b. R.sub.1 =CH.sub.2 OSi(Me).sub.2 t--C.sub.4 H.sub.9, R.sub.2 =H; c. R.sub.1 =H, R.sub.2 =CH.sub.2 OSi(Me).sub.2 t--C.sub.4 H.sub.9 ; d. R.sub.1 =OSi(Me).sub.2 t--C.sub.4 H.sub.9, R.sub.2 =H; e. R.sub.1 =H, R.sub.2 =OSi(Me).sub.2 t--C.sub.4 H.sub.9 ; f. R.sub.1 =CH.sub.3, R.sub.2 =OSi(Me).sub.2 t--C.sub.4 H.sub.9.
Claim 14
Dependent Claim
7 words
A process of claim 10 wherein X=p-fluorobenzyloxy.
Claim 15
Dependent Claim
60 words
A process of claim 13 wherein the compound (III) prepared is selected from the group wherein: a. R.sub.1 =CH.sub.3, R.sub.2 =H; b. R.sub.1 =CH.sub.2 OSi(Me).sub.2 t--C.sub.4 H.sub.9, R.sub.2 =H; c. R.sub.1 =H, R.sub.2 =CH.sub.2 OSi(Me).sub.2 t--C.sub.4 H.sub.9 ; d. R.sub.1 =OSi(Me).sub.2 t--C.sub.4 H.sub.9, R.sub.2 =H; e. R.sub.1 =H, R.sub.2 =OSi(Me).sub.2 t--C.sub.4 H.sub.9 ; f. R.sub.1 =CH.sub.3, R.sub.2 =OSi(Me).sub.2 t--C.sub.4 H.sub.9.
Claim 16
Dependent Claim
20 words
A process of claim 7 wherein the catalyst is 1,5-cyclooctadiene(pyridine)(tricyclohexylphosphine)iridium(I)hexafluorophosphate and the solvent is a mixture of dichloromethane and isopropanol.
Claim 17
Dependent Claim
20 words
A process of claim 9 wherein the catalyst is 1,5-cyclooctadiene(pyridine)(tricyclohexylphosphine)iridium(I)hexafluorophosphate and the solvent is a mixture of dichloromethane and isopropanol.
Claim 18
Dependent Claim
20 words
A process of claim 12 wherein the catalyst is 1,5-cyclooctadiene(pyridine)(tricyclohexylphosphine)iridium(I)hexafluorophosphate and the solvent is a mixture of dichloromethane and isopropanol.
Claim 19
Dependent Claim
20 words
A process of claim 14 wherein the catalyst is 1,5-cyclooctadiene(pyridine)(tricyclohexylphosphine)iridium(I)hexafluorophosphate and the solvent is a mixture of dichloromethane and isopropanol.
References Cited (Backward Citations)
US4490546A
Cited
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| Annuity Stage | Window Opens | Payment Deadline | Surcharge Period Until | Estimated Fee | Status |
|---|---|---|---|---|---|
| 3.5 Years (Year 4) | 1992-10-23 | 1993-04-24 | 1993-10-24 | $2000.00 | Window Closed / Lapsed |
| 7.5 Years (Year 8) | 1996-10-23 | 1997-04-24 | 1997-10-24 | $3760.00 | Window Closed / Lapsed |
| 11.5 Years (Year 12) | 2000-10-23 | 2001-04-24 | 2001-10-24 | $7700.00 | Window Closed / Lapsed |