Citric Acid → HCID 67341828, compound

Participants

Reaction Steps

A solution of (S)-(+)-3-hydroxytetrahydrofuran (259 mg, 2.94 mmol) in dry NMP (1 mL) was added to a solution of KOtBu (271 mg, 2.42 mmol) in dry NMP (1 mL). The reaction was stirred at room temperature for 15 min, then a solution of 5-(3,3-dimethyl-but-1-ynyl)-3-(1-oxa-spiro[2.5]oct-6-ylamino]-thiophene-2-carboxylic acid methyl ester (200 mg, 0.576 mmol) in dry NMP (4.0 mL) was added and the reaction heated in a 40° C. oil bath for 24 h. The reaction was poured into ice water, cooled to 0° C., neutralized with 5% citric acid to pH=5-6 and extracted with ethyl acetate. The organic layer was washed with 5% LiCl, brine, dried and concentrated to give a brown oil which was taken up in dichloromethane/MeOH (5.0 mL/1.0 mL) and treated with the dropwise addition of TMSCH2N2 (0.35 mL, 0.692 mmol, 2M in hexane). After 20 min, volatiles were removed under vacuum and the crude residue was purified by column chromatography on silica gel (Teledyne Isco Redisep Rf Gold™) eluting with 100% dichloromethane to 20% ethyl acetate/dichloromethane to give 5-(3,3-dimethyl-but-1-ynyl)-3-[4-hydroxy-4-(tetrahydro-furan-3-yloxymethy)-cyclohexylamino]-thiophene-2-carboxylic acid methyl ester (120 mg, 48%) as a colorless solid.

Provenance & Evidence