US4584389A
Expired / Lapsed
US
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Processes for preparing 6(R)-[2-[8(S)(2,2-dimethylbutyryloxy)-2(S),6(S)-dimethyl-1,2,3,4,4a(S),5,6,7,8,8a(S)-decahydronaphthyl-1(S)]ethyl]-4(R)-hydroxy-3,4,5,6-tetrahydro-2H-pyran-2-one
Assignee: Merck and Co Inc
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Filing: 1985-05-23
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Granted: 1986-04-22
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Expires: 2005-05-23
Abstract
Abstract The compound 6(R)-[2-8(S)(2,2-dimethylbutyryloxy)-2(S),6(S)-dimethyl-1,2,3,4,4a(S),5,6,7,8,8a(S)-decahydronaphthyl-1(S)ethyl]-4(R)-hydroxy-3,4,5,6-tetrahydro-2H-pyran-2-one is prepared in two steps from mevinolin and comprise reduction of the two double bonds and C-methylation of the 8(S)-(2-methylbutyryloxy) group to form the 2,2-dimethylbutyryloxy group. The two steps can be performed in either order.
Inventors
- 👤 Meyer Sletzinger
- 👤 Thomas R. Verhoeven
- 👤 Ralph P. Volante
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-11-09 01:20
CPC Classifications
C; C07; C07D; C07D309/00; C07D309/16; C07D309/28; C07D309/30
Claims Analysis
Total Claims: 7
Claim 1
Independent Claim
119 words
A process for the preparation of a compound of structural formula: ##STR3## which comprises the steps in either order of (1) catalytic reduction of the two double bonds of the mevinolin molecule with a platinum on alumina catalyst in an organic solvent with agitation; and (2) C-methylation of the 2-methylbutryloxy side chain of the alkali metal salt of the mevinolin molecule with a methylating agent selected from methyl bromide, methyl chloride or methyl iodide and a strong base selected from alkali metal amide wherein the alkali metal is lithium, sodium or potassium and the amide is diethyl amide, pyrrolidide, dimethyl amide or diisopropyl amide and then relactonization with aqueous mineral acid selected from hydrochloric, hydrobromic, sulfuric or phosphoric acid.
Claim 2
Dependent Claim
119 words
A process for the preparation of a compound of structural formula: ##STR3## which comprises the steps in either order of (1) catalytic reduction of the two double bonds of the mevinolin molecule with a platinum on alumina catalyst in an organic solvent with agitation; and (2) C-methylation of the 2-methylbutryloxy side chain of the alkali metal salt of the mevinolin molecule with a methylating agent selected from methyl bromide, methyl chloride or methyl iodide and a strong base selected from alkali metal amide wherein the alkali metal is lithium, sodium or potassium and the amide is diethyl amide, pyrrolidide, dimethyl amide or diisopropyl amide and then relactonization with aqueous mineral acid selected from hydrochloric, hydrobromic, sulfuric or phosphoric acid.
Claim 3
Dependent Claim
18 words
The process of claim 1 wherein the two steps are in the order of reduction followed by C-alkylation.
Claim 4
Dependent Claim
91 words
The process of claim 1 wherein (1) the reduction step utilizes a 2-10% Pt/Al 2 O 3 catalyst; the solvent is selected from ethyl acetate, isopropyl acetate, hexanes, and methylene chloride; the hydrogen pressure is atmospheric or higher; and the temperature is 15°-40° C. (2) the C-methylation step is conducted with methyl iodide or methyl bromide in an ethereal solvent at -50° to -25° C. in the presence of an alkali metal amide wherein the alkali metal is sodium, potassium or lithium and the amide is diethylamide, dimethylamide, pyrrolidide or diisopropylamide.
Claim 5
Dependent Claim
18 words
The process of claim 3 wherein the two steps are in the order of reduction followed by alkylation.
Claim 6
Dependent Claim
54 words
The process of claim 3 wherein (1) the reduction step utilizes 5% Pt/Al 2 O 3 , ethyl acetate, and 40 psi of hydrogen, at 20°-25° C.; and (2) the C-methylation step utilizes methyl iodide or methyl bromide, in tetrahydrofuran, at -35° to -30° C. in the presence of lithium diethylamide or lithium pyrrolidide.
Claim 7
Dependent Claim
18 words
The process of claim 5 wherein the two steps are in the order of reduction followed by alkylation.
References Cited (Backward Citations)
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Cited
US3983140A
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US4231938A
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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) | 1989-04-21 | 1989-10-21 | 1990-04-22 | $2000.00 | Window Closed / Lapsed |
| 7.5 Years (Year 8) | 1993-04-21 | 1993-10-21 | 1994-04-22 | $3760.00 | Window Closed / Lapsed |
| 11.5 Years (Year 12) | 1997-04-21 | 1997-10-21 | 1998-04-22 | $7700.00 | Window Closed / Lapsed |