Diisopropylamine → 2-(2,4-difluorophenoxy)-3-hydroxy-3-[4-nitro-2-(2-trimethylsilanyl-ethoxymethyl)-2H-pyrazol-3-yl]propionic acid methyl ester

Participants

Reaction Steps

To a −78° C. solution of diisopropylamine (0.3 mL, 2.1 eq) in diethyl ether (3 mL) was added a 2.5 M solution of n-butyllithium in hexanes (Aldrich) (0.84 mL, 2.1 eq). The resulting mixture was stirred for 15 minutes. To this mixture was added a solution of (2,4-difluorophenoxy)acetic acid methyl ester (425 mg, 2.1 eq) in diethyl ether (2 mL) via a syringe, and the resulting mixture was stirred at −78° C. for 30 minutes, after which a solution of 4-nitro-2-(2-trimethylsilanyl-ethoxymethyl)-2H-pyrazole-3-carbaldehyde (271 mg, 1 mmol) in diethyl ether (2 mL) was added. The resulting mixture was stirred for 2 hours. The −78° C. reaction mixture was diluted with a saturated aqueous ammonium chloride solution, then diluted with ethyl acetate (150 mL) and water (25 mL). The organic layer was separated, washed with brine (1×50 mL), dried over magnesium sulfate, filtered and concentrated to give the crude product as an oil (709 mg). Purification of the crude product by Preparative Thin Layer Chromatography eluting with 25% ethyl acetate in hexanes gave the title compound as a diastereomeric mixture (257 mg, thick colorless oil). M+=473.

Provenance & Evidence