N-bromobutanimide → 3-(Bromomethyl)-5-chloro-1-benzothiophene

Participants

Reaction Steps

Reaction of chloroacetone with 4-chlorothiophenol gave (4-chlorophenyl)thiomethyl methyl ketone, which was cyclized by reaction with polyphosphoric acid to 5-chloro-3-methylbenzothiophene. Bromination of the latter compound by photochemical reaction with N-bromosuccinimide provided 5-chloro-3-bromomethylbenzothiophene, which was reacted with sodium cyanide to give 5-chloro-3-cyanomethylbenzothiophene. The latter compound was hydrolyzed and esterified to give methyl α-(5-chloro-3-benzothienyl)acetate. Reaction of the ester with sodium methoxide and n-butyl nitrite afforded methyl α-hydroxyimino-α-(5-chloro-3-benzothienyl)acetate. Reduction of the oxime by reaction with zinc and formic acid and subsequent reaction with di-tert.-butyl carbonate gave N-tert.-butoxycarbonyl-(5-chloro-3-benzothienyl)glycine. NMR (CDCl3): δ 1.1-1.5 (broad s, 9H); δ 5.4-5.7 (broad s, 1H); δ 7.2-8.0 (m, 4H).

Provenance & Evidence