METHOD FOR PRODUCING 6-METHYLENEHYDROCORTISONE OR ESTERS THEREOF FROM HYDROCORTISONE 21-ACETATE Russian patent published in 2018 - IPC C07J5/00 C07J75/00 

FIELD: chemistry.

SUBSTANCE: invention relates to a process for the preparation of 6-methylenehydrocortisone (11β,17α,21-trihydroxy-6-methylenepregn-4-ene-3,20-dione) or esters thereof of general formula I I, in which R=COCF₃ or H; R₁=COCH₃ or H, from hydrocortisone 21-acetate of formula II, through a series of conversions, comprising protection of the 11β-hydroxyl group by esterification with a trifluoroacetic acid derivative in an aprotic solvent medium under basic catalysis conditions using an effective amount of a catalyst to form 21-acetoxy-17α-hydroxy-11β-trifluoroacetyloxypregn-4-ene-3,20-dione of formula III, enol-esterification of the Δ⁴-3-keto system of the resulting compound by the action of a trialkyl orthoformate in the presence of an acid catalyst to form a 3-alkoxyester Δ^3,5-3-hydroxy derivative of general formula IV, condensing it with a reagent obtained from formaldehyde and a secondary amine in the presence of an acid catalyst to form a mixture of 6α- and 6β-isomers of the 6-(N-methyl-T-phenyl)-aminomethyl derivative of general formula V, cleavage of the resulting mixture of Mannich steroid bases on the C-N bond by the action of a protonic mineral acid in the presence of hydrohalic acid salts and removal of protecting groups 11β- and 21-hydroxyl groups entirely or in part. II, III, IV, V.

EFFECT: simple method of preparing a compound of general formula I from hydrocortisone 21-acetate with output of desired products of at least 80 %.

56 cl, 11 ex