Hydrochloric Acid → 4-Chloro-5-(1-hydroxy-propyl)-thiophene-2-carboxylic acid

Participants

Reaction Conditions

Reaction Steps

A solution of 4,5-dichloro-thiophene-2-carboxylic acid in THF (25 mL) at −53° C. is treated with LiHMDS (2.5 mL, 1 M THF) and then cooled to −78° C. for 10 min. Tert-butyl lithium (3.2 mL, 1.7 M Pentane, 5.4 mmol) is added dropwise for 12 min., then treated with propanal (0.25 mL, 3.4 mmol). After 5 min. the reaction is warmed to rt and stirred overnight. The reaction mixture is then acidified with 1 N HCl (10 mL) and extracted with EtOAc (3×25 mL). Combined organic extracts are dried over MgSO4, filtered, and concentrated to provide crude 4-chloro-5-(1-hydroxy-propyl)-thiophene-2-carboxylic acid as a brown syrup (0.280 g), which is used in the next step without further purification.

Provenance & Evidence