Process for preparation of 16 α-methyl corticoids from Δ16 -steroids

Claim 2

In a process for the preparation of a corticoid having the ring D of formula wherein R 21 is hydrogen, halogen or OR" wherein R" is hydrogen or a protecting group and where the improvement comprises (1) contacting a compound having the ring D of formula ##STR2## wherein R 21 is a defined above with methylmagnesium halide in the presence of a copper catalyst; (2) treating the reaction mixture of step (1) with a sulfinyl halide or mixed anhydride comprising an enol sulfinate; and (3) adding a thiophile to the reaction mixture of step (2) to obtain the corticoid.

Claim 3

A process for the preparation of a compound of the formula ##STR3## wherein is optionally a single or double bond with the proviso that when one of or is a double bond the other cannot be a double bond; R 3 is an (O), (H, α-OR) or (H, β-OR) wherein R is hydrogen or a protecting group; R 6 is hydrogen, methyl or fluoro; R 9 is hydrogen, fluoro, chloro or bromo; R 11 is (H), (H,H), (H, β-chloro), (O), (H, α-OR') or (H, β-OR'), wherein R' is hydrogen or a protecting group; R 21 is hydrogen, halogen or OR" wherein R" is hydrogen or a protecting group; which comprises: (1) contacting a compound of formula ##STR4## wherein , , R 3 , R 6 , R 9 , R 11 and R 21 are as defined above with methylmagnesium halide in the presence of a copper catalyst; (2) treating the reaction mixture of step (1) with aryl sulfinyl halide or mixed anhydrides to prepare an enol sulfinate; (3) adding a thiophile to the reaction mixture of step (2); to obtain the compound having formula IV.

Claim 4

A process for the preparation of a compound of the formula ##STR3## wherein is optionally a single or double bond with the proviso that when one of or is a double bond the other cannot be a double bond; R 3 is an (O), (H, α-OR) or (H, β-OR) wherein R is hydrogen or a protecting group; R 6 is hydrogen, methyl or fluoro; R 9 is hydrogen, fluoro, chloro or bromo; R 11 is (H), (H,H), (H, β-chloro), (O), (H, α-OR') or (H, β-OR'), wherein R' is hydrogen or a protecting group; R 21 is hydrogen, halogen or OR" wherein R" is hydrogen or a protecting group; which comprises: (1) contacting a compound of formula ##STR4## wherein , , R 3 , R 6 , R 9 , R 11 and R 21 are as defined above with methylmagnesium halide in the presence of a copper catalyst; (2) treating the reaction mixture of step (1) with aryl sulfinyl halide or mixed anhydrides to prepare an enol sulfinate; (3) adding a thiophile to the reaction mixture of step (2); to obtain the compound having formula IV.

Claim 5

A claim according to claim 2 wherein R 3 is (O), R 6 is in the α-position, , is a double bond, is a single bond, R 11 is attached to the ring by a single bond and is a hydrogen, α-OR' or β-OR' with the proviso that if R 11 is OR' then the in ring C is a single bond, and R 21 is OR".

Claim 6

A process according to claim 2 wherein the compound having formula IV prepared is 17α-,21-dihydroxy-16α-methylpregna-4,9(11)diene-3,20-dione 21-acetate.

Claim 7

A process according to claim 2 wherein the compound having formula IV prepared is 17α-,21-dihydroxy-16α-methylpregna-1,4,9(11)-triene-3,20-dione-21-acetate.

Claim 8

A process of claim 2 wherein the copper catalyst is cuprous iodide, cuprous bromide-dimethyl sulfide complex or cupric acetate monohydrate.

Claim 9

A process of claim 2 wherein the sulfinyl radical source is aryl-sulfinyl chloride or a mixed anhydride comprising the reaction product of p-toluene sulfinic acid or benzene sulfinic acid and trifluoro or trichloro acetic anhydride.

Claim 10

A process of claim 7 wherein the sulfinyl radical source is phenylsulfinyl chloride or p-tolylsulfinylchloride.

Claim 11

A process of claim 7 wherein the thiophile is sodium methyl xanthate or sodium thiocyanate.