US3891631A
Expired / Lapsed
US
⏱️ 0.0 years remaining
Process for preparing 17{60 -monoesters of 17{60 , 21-dihydroxy-20-oxo steroids
Assignee: Glaxo Laboratories Ltd
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Filing: 1973-08-10
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Granted: 1975-06-24
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Expires: 1993-08-10
Abstract
Abstract The specification describes a process for preparing 17 Alpha carboxylate or neutral phosphate or carbonate esters of 17 Alpha -21-dihydroxy-20-oxo steroids wherein a 21-carboxylate or neutral phosphate or carbonate ester of a 17 Alpha ,21-dihydroxy-20-oxosteroid is treated with a non-hydroxylic base in an anhydrous aprotic medium to remove a proton selectively from the 17 Alpha hydroxyl grouping, and the reaction mixture neutralised or acidified whereby the intermediate product is protonated. The base used in the process can be for example a carbanionoid e.g. alkali metal alkyl, or metal amide, e.g. alkali metal amide, base. The process is applicable to the preparation of a wide variety of 17-esters of the above-mentioned type. The process can also be used to prepare certain enol-aldehydes corresponding to the above-described 17-ester, a particular class of these enolaldehydes being described in the specification as novel compounds.
Inventors
- 👤 Gordon Hanley Phillipps
- 👤 Brian Macdonald Bain
- 👤 Graham Durrant
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-11-02 18:14
CPC Classifications
C; C07; C07F; C07F1/00; C07F1/005; C07F1/08; C07F9/00; C07F9/02; C07F9/06; C07F9/08
Claims Analysis
Total Claims: 25
Claim 1
Independent Claim
72 words
A PROCESS FOR THE PREPARATION OF 17A-CARBOXYLATE OR NEUTRAL PHOSPHATE OR CARBONATE ESTERS OF 17A,21-DIHYDROXY20-OXO-STEROIDS WHICH COMPRISES REACTING A 21-CARBOXYLATE OR NEUTRAL PHOSPHATE OR CARBONATE ESTER OF A 17A,21-DIHYDROXY20-OXO-STEROID WITH A NON-HYDROXYLIC BASE IN AN ANHYDROUS APROTIC MEDIUM TO REMOVE A PROTON SELECTIVELY FROM THE 17AHYDROXYL GROUPING WITHOUT ELIMINATION OF THE 17A-OXYGEN FUNCTION, AND SUBSEQUENTLY NEUTRALISING OF ACIDIFYING THE REACTION MIXTURE WHEREBY THE INTERMEDIATE PRODUCT IS PROTONATED TO PRODUCE THE DESIRED 17A-ESTER.
Claim 2
Dependent Claim
72 words
A PROCESS FOR THE PREPARATION OF 17A-CARBOXYLATE OR NEUTRAL PHOSPHATE OR CARBONATE ESTERS OF 17A,21-DIHYDROXY20-OXO-STEROIDS WHICH COMPRISES REACTING A 21-CARBOXYLATE OR NEUTRAL PHOSPHATE OR CARBONATE ESTER OF A 17A,21-DIHYDROXY20-OXO-STEROID WITH A NON-HYDROXYLIC BASE IN AN ANHYDROUS APROTIC MEDIUM TO REMOVE A PROTON SELECTIVELY FROM THE 17AHYDROXYL GROUPING WITHOUT ELIMINATION OF THE 17A-OXYGEN FUNCTION, AND SUBSEQUENTLY NEUTRALISING OF ACIDIFYING THE REACTION MIXTURE WHEREBY THE INTERMEDIATE PRODUCT IS PROTONATED TO PRODUCE THE DESIRED 17A-ESTER.
Claim 3
Dependent Claim
14 words
A process as claimed in claim 1 wherein the base is a carbanionoid base.
Claim 4
Dependent Claim
14 words
A process as claimed in claim 2 wherein the base is a lithium alkyl.
Claim 5
Dependent Claim
29 words
A process as claimed in claim 2 wherein the base is a lithium diloweralkyl cuprate, an alkali metal triloweralkyl cobalt, an alkali metal triloweralkyl manganese, or a lower-alkyl lithium.
Claim 6
Dependent Claim
25 words
A process as claimed in claim 4 wherein the base is lithium dimethyl cuprate, lithium trimethyl cobalt, lithium trimethyl manganese, methyl lithium or n-butyl lithium.
Claim 7
Dependent Claim
16 words
A process as claimed in claim 1 wherein the base is an alkali metal amide base.
Claim 8
Dependent Claim
30 words
A process as claimed in claim 6 wherein the base is an alkali metal bis-(triloweralkyl-silyl)amide, or an alkali metal amide carrying one or two alkyl or cycloalkyl groups as N-substituents.
Claim 9
Dependent Claim
25 words
A process as claimed in claim 7 wherein the base is lithium or sodium bis-(trimethyl -sily)-amide, lithium diethylamide, lithium N-isopropylcyclohexyl-amide, lithium dicyclohexylamide or lithium di-isopropylamide.
Claim 10
Dependent Claim
16 words
A process as claimed in claim 1 wherein the base is an alcoholate or phenolate base.
Claim 11
Dependent Claim
13 words
A process as claimed in claim 9 wherein the base is potassium tert-butoxide.
Claim 12
Dependent Claim
22 words
A process as claimed in claim 1 wherein the neutralisation or acidification of the reaction mixture is effected in an anhydrous medium.
Claim 13
Dependent Claim
22 words
A process as claimed in claim 2 wherein the neutralisation or acidification of the reaction mixture is effected in an aqueous medium.
Claim 14
Dependent Claim
106 words
A process as claimed in claim 1 wherein the said 17 Alpha , 21-dihydroxy-20-oxo-steroid contains at least one of the following substitents: hydroxy groups or oxo-groups or protected hydroxy or oxo groups at at least one of positions 3- and 11-; at least one of an alkyl group or a halogen atom at at least one of positions 2- and 6-; a halogen atom at at least one of the 9 Alpha -, 11 Beta -or 9 Alpha , 12 Alpha -positions; an alkyl group or an alkylidene group at the 16-positions and an alkyl group at at least one of the 10-, 13- and 21-positions.
Claim 15
Dependent Claim
35 words
A process as claimed in claim 1 wherein the said 17 Alpha , 21-dihydroxy-20-oxo-steroid is hydrocortisone, cortisone, dexamethasone, beclomethasone, betamethasone, prednisolone, prednisone, 16 Beta -methyl- Delta 8-prednisolone, 11-dehydrobetamethasone, 6 Alpha -bromo-betamethasone or 9 Alpha -fluoro-16-methylene-prednisolone.
Claim 16
Dependent Claim
24 words
A process as claimed in claim 1 wherein the said 21-ester used as starting material is an aliphatic, cycloaliphatic, araliphatic or aromatic carboxylate ester.
Claim 17
Dependent Claim
50 words
A process as claimed in claim 15 wherein the said 21-ester is an alkanoate ester; an alkanoate ester, the alkyl radical of which is substituted by at least one halogen atom or by a morpholino group; a cycloalkylalkanoate or cycloalkanoate ester; an aralkanoate ester; or a monocyclic aromatic carboxylate ester.
Claim 18
Dependent Claim
44 words
A process as claimed in claim 16 wherein the said 21-ester is a C1-6 alkanoate ester; a C4-12 cycloalkyl-alkanoate or cycloalkanoate ester; or an aralkanoate ester, the 21-ester group containing 1 to 6 carbon atoms in the aliphatic moiety and a monocyclic aromatic moiety.
Claim 19
Dependent Claim
27 words
A process as claimed in claim 17 wherein the said 21-ester is an acetate, propionate, iso-butyrate, n-butyrate, tert-butylacetate, valerate, pivalate, morpholinoacetate, trichloroacetate, cyclohexylcarboxylate, adamantoate, or benzoate esTer.
Claim 20
Dependent Claim
22 words
A process as claimed in claim 2 wherein the base is a lithium loweralkyl loweralkoxy cuprate or a lithium loweralkyl cyano cuprate.
Claim 21
Dependent Claim
24 words
A process as claimed in claim 2 wherein neutralisation or acidification of the reaction mixture is effected using anhydrous acetic acid or p-toluenesulphonic acid.
Claim 22
Dependent Claim
21 words
A process as claimed in claim 1 and wherein the reaction mixture is treated with water after said neutralisation or acidification.
Claim 23
Dependent Claim
23 words
A process as claimed in claim 17 wherein the said 21-ester is a formate, p-chloro-benzoate, o-acetoxy-benzoate, o- or p-fluoro-benzoate, o-nitro-benzoate, o-hydroxy-benzoate or p-methoxy-benzoate.
Claim 24
Dependent Claim
11 words
A process for the preparation of a steroid having the grouping
Claim 25
Dependent Claim
11 words
A process for the preparation of a steroid having the grouping
References Cited (Backward Citations)
USPTO Annuity & Maintenance Windows
| Annuity Stage | Window Opens | Payment Deadline | Surcharge Period Until | Estimated Fee | Status |
|---|---|---|---|---|---|
| 3.5 Years (Year 4) | 1978-06-23 | 1978-12-23 | 1979-06-24 | $2000.00 | Window Closed / Lapsed |
| 7.5 Years (Year 8) | 1982-06-23 | 1982-12-23 | 1983-06-24 | $3760.00 | Window Closed / Lapsed |
| 11.5 Years (Year 12) | 1986-06-23 | 1986-12-23 | 1987-06-24 | $7700.00 | Window Closed / Lapsed |