Thionyl Chloride → 3-Oxoandrost-4-ene-17beta-carbonyl chloride

Participants

Reaction Steps

U.S. Pat. No. 5,565,467 disclosed Dutasteride and process for preparation. According to U.S. Pat. No. '467, Dutasteride may be prepared by reacting 3-oxo-4-androstene-17β-carboxylic acid (II) with thionyl chloride in presence of pyridine to produce 3-oxo-4-androstene-17β-carboxylic acid chloride (IIa), which is further reacted with 2,5-bis(trifluoromethyl)aniline (III) to produce 17β-N-[2,5-bis(trifluoromethyl)-phenyl]carbomoyl-1-androst-4-en-3-one (IV). Oxidation of 17β-N-[2,5-bis(trifluoromethyl)phenyl]carbomoyl-1-androst-4-en-3-one (IV) by treating with aqueous sodium permanganate and sodium periodate under basic conditions produce 17β-N-[2,5-bis(trifluoromethyl)phenyl]carbamoyl-5-oxo-A-nor-3,5-secoandrostan-3-oic acid (V), which is further treated with ammonia in ethylene glycol, followed by hydrogenation to produce 17β-N-[2,5-bis(trifluoromethyl)phenyl]carbamoyl-4-aza-5α-androstan-3-one (VI). Dehydrogenating a compound (VI) using 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ) and bis(trimethylsilyl)trifluoroacetamide in dry dioxane to produce Dutasteride (I).

Provenance & Evidence