Patent GB-792562-A (GB)
Title: Manufacture of new esters of the steroid series
IPC: C07J5/00
Filed: 1954-07-28
Abstract: The invention comprises 11-trifluoracetoxy steroids and a process for their preparation by treatment of an 11-hydroxy steroid with trifluoracetic acid or a reactive functional derivative thereof capable of acylating a free hydroxy group (e.g. the anhydride or acid chloride), optionally in the presence of a basic catalyst (e.g. pyridine).  The process may be used for the protection of an 11-hydroxy group during a steroid synthesis, the 11-trifluoracetate being readily hydrolysed (e.g. with acid or alkaline agents at about 0 DEG  C.) after the desired synthesis steps have been carried out, after which still further process steps may be carried out, if desired.  If the starting material also contains a 3-hydroxy group, this is esterified at the same time as the 11-hydroxy group, and the 3-trifluoracetoxy group can subsequently be selectively hydrolysed, e.g. by the action of water or a dilute solution of an alkaline bicarbonate in aqueous methanol.  In examples: (1) D 4-3-keto - 11a - trifluoracetoxyetiocholenic acid methyl ester is prepared by the action of trifluoracetic anhydride in dioxan in the cold on D 4-3-keto-11a -hydroxyetiocholenic acid methyl ester, or on the free acid with subsequent treatment of the product with diazomethane in ether; the free acid corresponding to the product may be converted to 11-epicorticosterone 21-monoacetate by reaction with oxalyl chloride in benzene, treatment of the product with diazomethane, isolation of 11a -trifluoracetoxy-21-diazopregesterone by chromatography, hydrolysis of the trifluoracetoxy group with aqueous methanolic potassium bicarbonate solution, and treatment of the product with glacial acetic acid at 100-105 DEG  C.; (2) 3b  : 11b -dihydroxyetioallocholanic acid methyl ester is diesterified with trifluoracetic anhydride in the cold in the presence or absence of pyridine, and the 3-trifluoracetoxy group is selectively hydrolysed with cold aqueous methanolic potassium bicarbonate solution; 3b -acetoxy-11b -hydroxyetioallocholanic acid methyl ester may be similarly esterified; (3) 3b -acetoxy-11b -hydroxyetioallocholanic acid is esterified as in (2) (in the presence of pyridine); the product may be converted by a process analogous to that of (1) into 3b  : 21 - diacetoxy - 11b  - hydroxy - 20 - ketoallopregnane; (4) the process of (1) (as applied to the free acid) is repeated with the 11b -isomer, yielding finally corticosterone 21-monoacetate; (5) D 4 - 11b  : 17a  - dihydroxy - 21 - acetoxy - 3 : 20 - diketopregnane is esterified as in (1) and the product partially hydrolysed as in (2) and finally acetylated, forming D 4 - 17a  - hydroxy - 11b  - trifluoracetoxy - 21 - acetoxy - 3 : 20 - diketopregnene; (6) 3a  : 11b  : 17a  - trihydroxy-20-ketopregnane is esterified as in (2) (without pyridine), the 3- and 17-trifluoracetoxy groups are selectively hydrolysed as in (2), the product is brominated and acetoxylated in the 21-position, the 3-hydroxy group is oxidized to keto with N-bromosuccinimide or chromic acid, and a D 4-double bond is introduced by bromination in the 4-position, splitting off HBr using semi-carbazide hydrochloride and splitting the semi-carbazone with pyruvic acid, and finally the product is hydrolysed to D 4-11b : 17a  : 21-trihydroxy-3 : 20-diketopregnene.