U.S. Pat. No. 4,335,121, British patents GB 2,088,877, GB 2,137,206, U.S. Pat. No. 4,578,221 and J. Med. Chem., 1994, 37, 3717-3729, describe the 17α-propionylation of compound [I], to obtain the fluticasone propionate intermediate [III], through the two chemical steps illustrated below, via the mixed anhydride compound [IV].

In the first step (a), the mixed anhydride [IV] is prepared with an excess of at least 2 moles of propionyl chloride per mol of compound [I], in the presence of triethylamine and using dichloromethane as solvent. Upon conclusion of the propionylation reaction, the reaction mixture is worked-up and a buff solid is obtained. In the second step (b), this solid is dissolved in acetone and treated with diethylamine, to convert the mixed anhydride to compound [III]. Once the aminolysis reaction is complete, the reaction mixture is worked up to isolate compound [III].
International patent application WO 03/066654 claims the preparation of intermediate [III] by: (a) reacting compound [I] with at least 1.3 moles of an activated derivative of propionic acid per mol of compound [I], and removal of the sulphur linked moiety from any compound of formula [IV] with an organic primary or secondary amine such as diethanolamine or N-methylpiperazine.
Patent application WO 01/62722 discloses the 17α-esterification of the hydroxyacid compound [V] with an alkanoyl halide, in presence of a base, and particularly describes the preparation of the 17α-propionate compound of formula [VI]
by: (a) reacting the hydroxyacid of formula [V] with 2.3 moles of propionyl chloride per mol of compound [V], using triethylamine as base, and (b) in situ reacting the compound obtained in (a) with diethylamine.
All of the 17α-acylation procedures described in the prior art, either for the carbothioic acid [I] or the related carboxylic acid [V], use an excess of the acylating agent to ensure completion of the 17α-acylation, thus requiring aminolysis, with an adequate primary or secondary amine, of any mixed anhydride formed.