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

HRID 1044817Notes

Reaction equation

HRID 1044817 reaction equation
C[C@@]12[C@@H](C(NC3C=C(C(F)(F)F)C=CC=3C(F)(F)F)=O)CC[C@H]1[C@@H]1CC[C@H]3NC(=O)C=C[C@]3(C)[C@H]1CC2.[O:38]=[C:39]1[CH2:56][CH2:55][C@@:54]2([CH3:57])[C:41]([CH2:42][CH2:43][C@@H:44]3[C@@H:53]2[CH2:52][CH2:51][C@@:49]2([CH3:50])[C@H:45]3[CH2:46][CH2:47][C@@H:48]2[C:58]([OH:60])=O)=[CH:40]1.S(Cl)([Cl:63])=O>N1C=CC=CC=1>[O:38]=[C:39]1[CH2:56][CH2:55][C@@:54]2([CH3:57])[C:41]([CH2:42][CH2:43][C@@H:44]3[C@@H:53]2[CH2:52][CH2:51][C@@:49]2([CH3:50])[C@H:45]3[CH2:46][CH2:47][C@@H:48]2[C:58]([Cl:63])=[O:60])=[CH:40]1

Participants

5

Reactant 3

HCID 24386Thionyl ChlorideHCID 99472(17beta)-3-Oxoandrost-4-ene-17-carboxylic acidHCID 6918296Dutasteride2×

Product 1

HCID 117273863-Oxoandrost-4-ene-17beta-carbonyl chloride

Reagents, catalysts & solvents 1

HCID 1049PyridineSolvent

Procedure

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).

Sources & evidence

ORD record
ord-e1da9663aedc48d6854d0eb6715c8fb3
Source dataset
uspto-grants-2013_10
Patent number
US08563728B2

Reaction notes

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