US4582915A
Expired / Lapsed
US
⏱️ 0.0 years remaining
Process for C-methylation of 2-methylbutyrates
Assignee: Merck and Co Inc
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Filing: 1985-05-23
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Granted: 1986-04-15
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Expires: 2005-05-23
Abstract
Abstract Mevinolin, compactin and dihydro- and tetrahydro derivatives thereof are converted to more active HMG-CoA reductase inhibitors by C-methylation of the natural 2(S)-methylbutyryloxy side chain to form a 2,2-dimethylbutyryloxy side chain.
Inventors
- 👤 Meyer Sleteinger
- 👤 Thomas R. Verhoeven
- 👤 Ralph P. Volante
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-10-23 13:29
CPC Classifications
C; C07; C07D; C07D309/00; C07D309/16; C07D309/28; C07D309/30
Claims Analysis
Total Claims: 7
Claim 1
Independent Claim
132 words
A process for the preparation of a compound of the structural formula IIA: ##STR5## wherein: R 3 is methyl; R 4 is hydrogen, methyl or hydroxy; and the dotted lines represent possible double bonds in the 3,4-position, in the 3, 4 and 4a, 5 position or there are no double bonds. which comprises treatment of a compound of the structural formula (Ia): ##STR6## as its alkali metal salt with a methyl halide and an alkali metal amide of the formula M.sup.+ N.sup.- R.sup.1 R.sup.2 wherein M + is a cation derived from sodium, potassium or lithium, and R 1 and R 2 are C 1-3 alkyl or when taken together with the nitrogen atom to which they are attached form a 5 or 6 membered heterocyclic ring; followed by acidification and lactonization.
Claim 2
Dependent Claim
132 words
A process for the preparation of a compound of the structural formula IIA: ##STR5## wherein: R 3 is methyl; R 4 is hydrogen, methyl or hydroxy; and the dotted lines represent possible double bonds in the 3,4-position, in the 3, 4 and 4a, 5 position or there are no double bonds. which comprises treatment of a compound of the structural formula (Ia): ##STR6## as its alkali metal salt with a methyl halide and an alkali metal amide of the formula M.sup.+ N.sup.- R.sup.1 R.sup.2 wherein M + is a cation derived from sodium, potassium or lithium, and R 1 and R 2 are C 1-3 alkyl or when taken together with the nitrogen atom to which they are attached form a 5 or 6 membered heterocyclic ring; followed by acidification and lactonization.
Claim 3
Dependent Claim
26 words
The process of claim 1 which comprises treatment of Compound Ia with methyl iodide or methyl bromide in an ethereal solvent at -60° to -25° C.
Claim 4
Dependent Claim
29 words
The process of claim 2 wherein the ethereal solvent is tetrahydrofuran, the temperature is -35° to -30° C. and the alkali metal amide is lithium diethylamide or lithium pyrrolidide.
Claim 5
Dependent Claim
14 words
The process of claim 1 for the preparation of the compound of formula: ##STR7##
Claim 6
Dependent Claim
14 words
The process of claim 2 for the preparation of the compound of formula: ##STR8##
Claim 7
Dependent Claim
14 words
The process of claim 3 for the preparation of the compound of formula: ##STR9##
References Cited (Backward Citations)
GB885044A
Cited
US3983140A
Cited
US4231938A
Cited
US4351844A
Cited
JPS57149247A
Cited
US4490546A
Cited
USPTO Annuity & Maintenance Windows
| Annuity Stage | Window Opens | Payment Deadline | Surcharge Period Until | Estimated Fee | Status |
|---|---|---|---|---|---|
| 3.5 Years (Year 4) | 1989-04-14 | 1989-10-14 | 1990-04-15 | $2000.00 | Window Closed / Lapsed |
| 7.5 Years (Year 8) | 1993-04-14 | 1993-10-14 | 1994-04-15 | $3760.00 | Window Closed / Lapsed |
| 11.5 Years (Year 12) | 1997-04-14 | 1997-10-14 | 1998-04-15 | $7700.00 | Window Closed / Lapsed |