US4490546A
Expired / Lapsed
US
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Process for 4a'(R),5'-dihydromevinolin
Assignee: Merck and Co Inc
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Filing: 1983-06-20
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Granted: 1984-12-25
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Expires: 2003-06-20
Abstract
Abstract Mevinolin is converted to its 4a',5'-dihydro derivative by a route involving protection of the 3',4'-double bond followed by reduction of the 4a',5'-double bond followed by deprotection of the 3',4'-positions.
Inventors
- 👤 Chan-Hwa Kuo
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-10-23 14:24
CPC Classifications
C; C07; C07D; C07D309/00; C07D309/16; C07D309/28; C07D309/30; C07D317/00; C07D317/08; C07D317/44
Claims Analysis
Total Claims: 9
Claim 1
Independent Claim
167 words
A process for the preparation of trans 4a',5'-dihydromevinolin comprising the steps of: (a) t-butyldimethylsilylation of mevinolin with t-butyldimethylsilyl chloride and an acid acceptor at about 20°-50° C. for about 2 to 16 hours to produce 2; ##STR3## (b) osmium tetroxide hydroxylation of 2 to produce 3 by treating 2 with OsO 4 in a mixture of pyridine base and a benzenoid aromatic solvent; ##STR4## (c) hydrogenation of the 4a',5'-double bond of 3 with hydrogen in the presence of a noble metal hydrogenation catalyst in a solvent to produce the glycol 4; ##STR5## (d) cyclic thionocarbonate formation to give 5, by treatment of 4 with 1,1'-thiocarbonyldiimidazole in a benzenoid aromatic solvent at about 50°-100° C. for about 15 to 60 minutes; ##STR6## (e) conversion of the thionocarbonate 5 to the silylated olefin 6 by treatment of 5 with triethylphosphite at reflux temperature for about 100 to 200 hours; ##STR7## (f) hydrolysis of the t-butyldimethylsilyl ether 6 with dilute mineral acid in a solvent to produce 4a'(R),5'-dihydromevinolin 7 ##STR8##
Claim 2
Dependent Claim
167 words
A process for the preparation of trans 4a',5'-dihydromevinolin comprising the steps of: (a) t-butyldimethylsilylation of mevinolin with t-butyldimethylsilyl chloride and an acid acceptor at about 20°-50° C. for about 2 to 16 hours to produce 2; ##STR3## (b) osmium tetroxide hydroxylation of 2 to produce 3 by treating 2 with OsO 4 in a mixture of pyridine base and a benzenoid aromatic solvent; ##STR4## (c) hydrogenation of the 4a',5'-double bond of 3 with hydrogen in the presence of a noble metal hydrogenation catalyst in a solvent to produce the glycol 4; ##STR5## (d) cyclic thionocarbonate formation to give 5, by treatment of 4 with 1,1'-thiocarbonyldiimidazole in a benzenoid aromatic solvent at about 50°-100° C. for about 15 to 60 minutes; ##STR6## (e) conversion of the thionocarbonate 5 to the silylated olefin 6 by treatment of 5 with triethylphosphite at reflux temperature for about 100 to 200 hours; ##STR7## (f) hydrolysis of the t-butyldimethylsilyl ether 6 with dilute mineral acid in a solvent to produce 4a'(R),5'-dihydromevinolin 7 ##STR8##
Claim 3
Dependent Claim
141 words
The process for the preparation of trans 4a',5'-dihydromevinolin comprising the steps of: (a) osmium tetroxide hydroxylation of 2 ##STR9## to produce 3 by treating 2 with OsO 4 in pyridine and a benzenoid aromatic solvent; ##STR10## (b) hydrogenation of the 4a',5'-double bond of 3 with hydrogen in the presence of a noble metal hydrogenation catalyst in a solvent to produce the glycol 4; ##STR11## (c) cyclic thionocarbonate formation to give 5, by treatment of 4 with 1,1'-thiocarbonyldiimidazole in a benzenoid aromatic solvent at about 50° to 100° C. for about 15 to 60 minutes; ##STR12## (d) conversion of the thionocarbonate 5 to the silylated olefin 6 by treatment of 5 with triethylphosphite at reflux temperature for about 100 to 200 hours; ##STR13## (e) hydrolysis of the t-butyldimethylsilyl ether 6 with dilute mineral acid in a solvent to produce 4a'(R),5'-dihydromevinolin 7 ##STR14##
Claim 4
Dependent Claim
141 words
The process for the preparation of trans 4a',5'-dihydromevinolin comprising the steps of: (a) osmium tetroxide hydroxylation of 2 ##STR9## to produce 3 by treating 2 with OsO 4 in pyridine and a benzenoid aromatic solvent; ##STR10## (b) hydrogenation of the 4a',5'-double bond of 3 with hydrogen in the presence of a noble metal hydrogenation catalyst in a solvent to produce the glycol 4; ##STR11## (c) cyclic thionocarbonate formation to give 5, by treatment of 4 with 1,1'-thiocarbonyldiimidazole in a benzenoid aromatic solvent at about 50° to 100° C. for about 15 to 60 minutes; ##STR12## (d) conversion of the thionocarbonate 5 to the silylated olefin 6 by treatment of 5 with triethylphosphite at reflux temperature for about 100 to 200 hours; ##STR13## (e) hydrolysis of the t-butyldimethylsilyl ether 6 with dilute mineral acid in a solvent to produce 4a'(R),5'-dihydromevinolin 7 ##STR14##
Claim 5
Dependent Claim
118 words
The process for the preparation of trans 4a',5'-dihydromevinolin comprising the steps of: (a) hydrogenation of the 4a',5'-double bond of 3 ##STR15## with hydrogen in the presence of a noble metal hydrogenation catalyst in a solvent to produce the glycol 4; ##STR16## (b) cyclic thionocarbonate formation to give 5, by treatment of 4 with 1,1'-thiocarbonyldiimidazole in a benzenoid aromatic solvent at about 50° to 100° C. for about 15 to 60 minutes; ##STR17## (c) conversion of the thionocarbonate 5 to the silylated olefin 6 by treatment of 5 with triethylphosphite at reflux temperature for about 100 to 200 hours; ##STR18## (d) hydrolysis of the t-butyldimethylsilyl ether 6 with dilute mineral acid in a solvent to produce 4a'(R),5'-dihydromevinolin 7 ##STR19##
Claim 6
Dependent Claim
118 words
The process for the preparation of trans 4a',5'-dihydromevinolin comprising the steps of: (a) hydrogenation of the 4a',5'-double bond of 3 ##STR15## with hydrogen in the presence of a noble metal hydrogenation catalyst in a solvent to produce the glycol 4; ##STR16## (b) cyclic thionocarbonate formation to give 5, by treatment of 4 with 1,1'-thiocarbonyldiimidazole in a benzenoid aromatic solvent at about 50° to 100° C. for about 15 to 60 minutes; ##STR17## (c) conversion of the thionocarbonate 5 to the silylated olefin 6 by treatment of 5 with triethylphosphite at reflux temperature for about 100 to 200 hours; ##STR18## (d) hydrolysis of the t-butyldimethylsilyl ether 6 with dilute mineral acid in a solvent to produce 4a'(R),5'-dihydromevinolin 7 ##STR19##
Claim 7
Dependent Claim
76 words
The process of claim 1 wherein: in Step (a) the acid acceptor is an organic base and the solvent is DMF; in Step (b) the benzenoid aromatic solvent is benzene; in Step (c) the catalyst is selected from platinum oxide, platinum on carbon, palladium on carbon, and Raney nickel; in Step (d) the benzenoid aromatic solvent is benzene; in Step (f) the hydrolysis is conducted with a mixture of acetic acid, THF and dilute hydrochloric acid.
Claim 8
Dependent Claim
61 words
The process of claim 2 wherein: in Step (a) the benzenoid aromatic solvent is benzene; in Step (b) the catalyst is selected from platinum oxide, platinum on carbon, palladium on carbon, and Raney nickel; in Step (c) the benzenoid aromatic solvent is benzene; in Step (e) the hydrolysis is conducted with a mixture of acetic acid, THF and dilute hydrochloric acid.
Claim 9
Dependent Claim
52 words
The process of claim 3 wherein in Step (a) the catalyst is selected from platinum oxide, platinum on carbon, palladium on carbon, and Raney nickel; in Step (b) the benzenoid aromatic solvent is benzene; in Step (d) the hydrolysis is conducted with a mixture of acetic acid, THF and dilute hydrochloric acid.
References Cited (Backward Citations)
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| Annuity Stage | Window Opens | Payment Deadline | Surcharge Period Until | Estimated Fee | Status |
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| 3.5 Years (Year 4) | 1987-12-25 | 1988-06-25 | 1988-12-25 | $2000.00 | Window Closed / Lapsed |
| 7.5 Years (Year 8) | 1991-12-25 | 1992-06-25 | 1992-12-25 | $3760.00 | Window Closed / Lapsed |
| 11.5 Years (Year 12) | 1995-12-25 | 1996-06-25 | 1996-12-25 | $7700.00 | Window Closed / Lapsed |