2-Acetylamino-5-formyl-4-trifluoromethyl-benzoic acid methyl ester → 2-Acetylamino-5-(1-hydroxy-butyl)-4-trifluoromethyl-benzoic acid methyl ester

Participants

Reaction Conditions

Reaction Steps

To a solution of 2-acetylamino-5-formyl-4-trifluoromethyl-benzoic acid methyl ester (1.52 g, 5.26 mmol) in absolute Et2O (52 mL), under argon, was added a solution of propylmagnesium chloride (2.0 M in Et2O, 5.3 mL, 11 mmol) over 5 min at 20° C. An immediate crystallisation occurred along with an exotherm. The reaction mixture was cooled to 20° C. using an ice/water bath. The reaction mixture was stirred at r.t. for 1 h then poured onto sat. aq NH4Cl and EtOAc. The pH was adjusted to 7 with sat. aq NH4Cl and the layers were separated. The organic phase was washed with brine, dried (Na2SO4), filtered and concentrated in vacuo. The residue was purified by flash column chromatography (25 g silica gel, hexanes/EtOAc (1:0→7:3)) to give product as colorless crystals (409 mg, 23%). m.p.: 97-101° C., ESI-MS: m/z 334 [M+H]+, m/z 332 [M−H]−.

Provenance & Evidence