Isopropyl chloroformate → Isopropyl 5-(2-hydroxyethyl)thiophene-2-carboxylate

Participants

Reaction Steps

A solution of n-butyllithium (37 mL of a 1.6 M solution in hexanes, 59.2 mmol) was added slowly to a solution of tert-butyldimethyl(2-(thiophen-2-yl)ethoxy)silane (see U.S. Pat. No. 5,739,141; 9.5 g, 39.0 mmol) in THF (100 mL) at −78° C. After 1 h at −78° C., isopropyl chloroformate (60 mL of a 1.0 M solution in toluene, 60 mmol) was added slowly. After 1 h at −78° C., the reaction was quenched by addition of saturated aqueous NH4Cl (150 mL) and was allowed to warm to room temperature. The phases were separated and the organic phase was dried (Na2SO4), filtered (washing with excess THF) and concentrated in vacuo. The crude residue was dissolved in THF (100 mL), cooled to 0° C. and treated with tetrabutylammonium fluoride (43 mL of a 1.0 M solution in THF, 43 mmol). The reaction was allowed to warm to room temperature and was stirred overnight. The reaction was concentrated in vacuo, saturated aqueous NH4Cl (100 mL) was added and the mixture was extracted with EtOAc (3×150 mL). The combined extracts were washed with brine (100 mL), dried (Na2SO4), filtered and concentrated in vacuo. The crude residue was purified on 330 g silica (40% EtOAc/hexanes→60% EtOAc/hexanes, gradient) to afford 6.6 g (71%) of isopropyl 5-(2-hydroxyethyl)thiophene-2-carboxylate.

Provenance & Evidence