METHOD OF PREPARATION 6α-METHYLHYDROCORTISONE 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 6α-methylhydrocortisone (11β, 17α, 21-trihydroxy-6α-methylpregn-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 under basic catalysis conditions to form 21-acetoxy-17α-hydroxy-11β-trifluoroacetyloxypregn-4-ene-3,20-dione of formula III, enol-esterification of a Δ⁴-3-keto system of the resulting compound by the action of a trialkyl orthoformate in the presence of an acidic catalyst to form a 3-alkoxyester of a Δ^3,5-3-hydroxy derivative of general formula IV, condensing it with a Mannich reagent in the presence of an acid catalyst to form a mixture of 6α- and 6β-isomers of 6-(N-methyl-N-phenyl)-aminomethyl derivative of general formula V, cleavage of the resulting mixture of steroid Mannich bases on the C-N bond with the action of a mineral acid in the presence of hydrohalic acid salts to form a 6-methylene derivative of formula VI, isomerisation of the 6-exomethylene bond to the 6,7-endomethylene bond to form compound VII; catalytic hydrogenation of the 6,7-endomethylene bond to form a mixture of 6α-methyl- and 6β-methyl isomers and subsequent isomerisation of 6β-methyl isomer to a 6α-methyl derivative of formula VIII, removal of protective groups 11β- and 21-hydroxyl groups entirely or in part. II, III, IV, V, VI, VII, VIII.

EFFECT: simple method for preparing a compound of formula I from hydrocortisone 21-acetate with output of desired products not less than 80 %.

23 cl, 12 ex