US 5,670,676 AGranted

Process for preparation of 9.alpha. -chloro-11.beta. formyloxypregna-3.20-diones

AssigneeSchering Corporation

InventorsRichard W. Draper, Eugene J. Vater

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Abstract

Disclosed is a process for producing a compound of the formula: ##STR1## by reacting a compound of the formula: ##STR2## with: (1) a chlorinating reagent selected from an N-chloroimide or an N-chloroamide; (2) an anhydrous strong acid selected from orthophosphoric acid, alkylsulfonic acids, fluoroalkylsulfonic acids or arylsulfonic acids; and (3) anhydrous dimethylformamide; at a temperature within the range of about -78.degree. to about 0.degree. C.

Claims22

Dependent claims

A process for producing a compound of the formula:

##STR21## wherein:
the broken lines represent optional bonds;
R.sup.1 represents a acyl radical of:
(1) a hydrocarbon carboxylic acid having 2 to 12 carbon atoms;
or (2) benzoic acid substituted by a halogen or methoxy group;
R.sup.2 is selected from hydroxy or --OR.sup.6 ;
R.sup.3 is selected from hydrogen, lower alkyl, or .alpha.--OR.sup.7 ;
or R.sup.2 and R.sup.3 taken together represent a 16.alpha., 17.alpha.-lower alkylidenedioxy having up to 13 carbon atoms;
R.sup.4 is selected from hydrogen, .alpha.-methyl, .alpha.-bromo, .alpha.-chloro, .alpha.-fluoro, .beta.-fluoro and .alpha.fluoromethyl;
R.sup.5 is selected from hydrogen, methyl, fluorine, chlorine and bromine;
R.sup.6 is an acyl radical of:
(1) a hydrocarbon carboxylic acid having from 2 to 12 carbon atoms;
(2) an aromatic carboxylic acid wherein said aromatic group contains from 6 to 12 carbon atoms;
(3) an arylhydrocarbon carboxylic acid wherein said aryl group contains from 6 to 12 carbon atoms, and said hydrocarbon carboxylic acid group represents a straight or branched chain carboxylic acid having from 2 to 12 carbon atoms;
(4) a heteroaromatic carboxylic acid having at least one oxygen atom in the heteroaryl ring and wherein oxygen is the only heteroatom in the heteroaryl ring, and wherein the aromatic heterocyclic group contains from 2 to 14 carbon atoms;
or (5) a heteroaryl-hydrocarbon carboxylic acid having at least one oxygen atom in the heteroaryl ring and wherein oxygen is the only heteroatom in the heteroaryl ring, and wherein the aromatic heterocyclic group contains from 2 to 14 carbon atoms, and said hydrocarbon carboxylic acid group represents a straight or branched chain carboxylic acid having from 2 to 12 carbon atoms;
said acyl radical having from 2 to 12 carbon atoms;
and
R.sup.7 is an acyl radical of a hydrocarbon carboxylic acid having from 2 to 12 carbon atoms;
said process comprising reacting, under anhydrous conditions and under an inert atmosphere, a compound of the formula:
##STR22## wherein R.sup.1, R.sup.2, R.sup.3, R.sup.4, and R.sup.5 are as defined above, with:
(1) a chlorinating reagent selected from an N-chloroimide or an N-chloroamide;
(2) an anhydrous strong acid selected from orthophosphoric acid, alkylsulfonic acids, fluoroalkylsulfonic acids or arylsulfonic acids;
and (3) anhydrous dimethyl formamide;
said reaction being conducted at a temperature within the range of about -78.degree. to about 0.degree. C.

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Dependencies are inferred from the claim text.

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Abstract

A process for producing a compound of the formula:

##STR21## wherein:
the broken lines represent optional bonds;
R.sup.1 represents a acyl radical of:
(1) a hydrocarbon carboxylic acid having 2 to 12 carbon atoms;
or (2) benzoic acid substituted by a halogen or methoxy group;
R.sup.2 is selected from hydroxy or --OR.sup.6 ;
R.sup.3 is selected from hydrogen, lower alkyl, or .alpha.--OR.sup.7 ;
or R.sup.2 and R.sup.3 taken together represent a 16.alpha., 17.alpha.-lower alkylidenedioxy having up to 13 carbon atoms;
R.sup.4 is selected from hydrogen, .alpha.-methyl, .alpha.-bromo, .alpha.-chloro, .alpha.-fluoro, .beta.-fluoro and .alpha.fluoromethyl;
R.sup.5 is selected from hydrogen, methyl, fluorine, chlorine and bromine;
R.sup.6 is an acyl radical of:
(1) a hydrocarbon carboxylic acid having from 2 to 12 carbon atoms;
(2) an aromatic carboxylic acid wherein said aromatic group contains from 6 to 12 carbon atoms;
(3) an arylhydrocarbon carboxylic acid wherein said aryl group contains from 6 to 12 carbon atoms, and said hydrocarbon carboxylic acid group represents a straight or branched chain carboxylic acid having from 2 to 12 carbon atoms;
(4) a heteroaromatic carboxylic acid having at least one oxygen atom in the heteroaryl ring and wherein oxygen is the only heteroatom in the heteroaryl ring, and wherein the aromatic heterocyclic group contains from 2 to 14 carbon atoms;
or (5) a heteroaryl-hydrocarbon carboxylic acid having at least one oxygen atom in the heteroaryl ring and wherein oxygen is the only heteroatom in the heteroaryl ring, and wherein the aromatic heterocyclic group contains from 2 to 14 carbon atoms, and said hydrocarbon carboxylic acid group represents a straight or branched chain carboxylic acid having from 2 to 12 carbon atoms;
said acyl radical having from 2 to 12 carbon atoms;
and
R.sup.7 is an acyl radical of a hydrocarbon carboxylic acid having from 2 to 12 carbon atoms;
said process comprising reacting, under anhydrous conditions and under an inert atmosphere, a compound of the formula:
##STR22## wherein R.sup.1, R.sup.2, R.sup.3, R.sup.4, and R.sup.5 are as defined above, with:
(1) a chlorinating reagent selected from an N-chloroimide or an N-chloroamide;
(2) an anhydrous strong acid selected from orthophosphoric acid, alkylsulfonic acids, fluoroalkylsulfonic acids or arylsulfonic acids;
and (3) anhydrous dimethyl formamide;
said reaction being conducted at a temperature within the range of about -78.degree. to about 0.degree. C.

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