Preparation of corticoids from 17-keto steroids

Abstract

Disclosed is a 20,21-dihalo steroid (VII) and a steroidal sulfoxide (VIII) as well as processes to produce them. The 20,21-dihalo steroid (VII) and sulfoxide (VIII) are intermediates useful in the preparation of pharmaceutically useful corticoids.

Description

Claims

1. A 20,21-dihalo steroid of the formula ##STR1## where A is a fluorine, chlorine or bromine atom; M is a fluorine, chlorine or bromine atom; R.sub.6 is a hydrogen or fluorine atom or methyl group; R.sub.9 is a hydrogen or fluorine atom, hydroxyl group, --OSi(R).sub.3 or nothing; R.sub.11 is (H), (H,H), (H, .beta.--OSi(R).sub.3, or (O); R.sub.16 is a hydrogen atom or methyl group; R.sub.22 is alkyl of 1 thru 5 carbon atoms, trichloromethyl, phenyl, phenyl substituted with 1-4 carbon atoms or substituted with 1 thru 3 nitro or trifluoromethyl groups, aralkyl of 7 thru 12 carbon atoms or --N---(R.sub.122).sub.2 or phthalimide; .about. indicates the attached group can be in either the .alpha. or .beta. configuration; is a single or double bond.

2. A 20,21-dihalo steroid according to claim 1 wherein A is a chlorine atom.

3. A 20,21-dihalo steroid according to claim 2 where A and M are both a chlorine atom.

4. A 20,21-dihalo steroid according to claim 1 where R.sub.22 is phenyl.

5. A 20,21-dihalo steroid of formula (VII) according to claim 1 where R.sub.6 and R.sub.16 are hydrogen atoms, where R.sub.9 is nothing and R.sub.11 is [H] which gives a .DELTA..sup.9,11 functionality in the C ring.

6. A 20,21-dihalo steroid according to claim 5 which is 20,21-dichloro-21-(phenylsulfinyl)pregna-4,9(11),17(20)-trien-3-one.

7. A sulfoxide of the formula ##STR2## where Z is --OR.sub.20 or SR.sub.20 ; and where A, R.sub.6, R.sub.9, R.sub.11, R.sub.16, R.sub.22, .about. and are defined in claim 1.

8. A sulfoxide according to claim 7 where A is a chlorine atom.

9. A sulfoxide according to claim 7 where Z is methoxy or phenoxy.

10. A sulfoxide according to claim 7 where R.sub.22 is phenyl.

11. A sulfoxide of formula (VIII) according to claim 7 where R.sub.6 and R.sub.16 are hydrogen atoms, where R.sub.9 is nothing and R.sub.11 is [H] which gives a .DELTA..sup.9,11 functionality in the C ring.

12. A sulfoxide according to claim 7 which is 21-chloro-20-methoxy-21-(phenylsulfinyl)pregna-4,9(11),17(20)-trien-3-one.

13. A process for the preparation of a 20,21-dihalo steroid of the formula ##STR3## which comprises (1) contacting a C21-steroid of the formula ##STR4## with a sulfenylating agent of the formula R.sub.22 --S--X (VI), where A, M, R.sub.6, R.sub.9, R.sub.11, R.sub.16, R.sub.22, .about. and are defined in claim 1 and where X is a chlorine or bromine atom, phenylsulfone, phthalimide or imidazole group.

14. A process according to claim 13, where for the 20,21-dihalo steroid (VII), R.sub.6 and R.sub.16 are hydrogen atoms, were R.sub.9 is nothing and R.sub.11 is [H] which gives a .DELTA..sup.9,11 functionality in the C ring.

15. A process according to claim 13 where for the sulfenylating agent, R.sub.22 --S--X, X is a chlorine or bromine atom, and R.sub.22 is a phenyl group.

16. A process according to claim 13 where the temperature range for the sulfenylation reaction is from about -80.degree. to about 25.degree..

17. A process for the preparation of a sulfoxide of the formula ##STR5## which comprises contacting a 20,21-dihalo steroid of the formula ##STR6## with an alkoxide or mercaptide of the formula OR.sub.20.sup..crclbar. or SR.sub.20.sup..crclbar., respectively, where A, M, R.sub.6, R.sub.9, R.sub.11, R.sub.16, R.sub.22, .about. and are defined in claim 1; and where Z is defined in claim 7, and where R.sub.20 is alkyl of 1 thru 4 carbon atoms or phenyl.

18. A process according to claim 17, where for the 21-halo steroid (VIII), R.sub.6 and R.sub.16 are hydrogen atoms, where R.sub.9 is nothing and R.sub.11 is [H] which gives a .DELTA..sup.9,.sup.11 functionality in the C ring.

19. A process according to claim 17, where the base is an alkoxide.

20. A process according to claim 19, where the alkoxide is methoxide or phenoxide.

21. A process according to claim 17, where the reaction with base is performed in a polar solvent.

22. A process according to claim 17, where 1.0 equivalents of base are used.