Citric Acid → HCID 67452511, compound

Participants

Reaction Steps

N,N-Dimethylamine (405.7 g, 9.0 mol) was blown in a solution of (D)-methyl lactate (469 g, 4.5 mol) in methanol (234 mL) at 0-15° C. and the solution was stirred in a sealed vessel at 60-65° C. for 24 hr. The reaction mixture was concentrated under reduced pressure to give (D)-N,N-dimethyl lactamide (525 g). To the solution of a part (109 g, 0.93 mol) of the obtained (D)-N,N-dimethyl lactamide in THF (97 mL) were successively added dropwise methanesulfonic acid (0.9 g, 9.4 mmol) and ethyl vinyl ether (74 g, 1.03 mol) at 15-20° C. and the mixture was stirred for 5 hr to give a solution of (2R)-N,N-dimethyl-2-O-(1-ethoxyethyl)lactamide in THF. Subsequently, to this amide solution was dropwise added a solution of 2,4-difluorophenylmagnesium bromide, which had been synthesized from 2,4-difluorobromobenzene (180 g, 0.93 mol) and magnesium (23 g, 0.95 mol) by a conventional method, in THF (485 mL) at room temperature. The mixture was stirred overnight. The reaction solution was flown into cooled aqueous ammonium chloride solution, neutralized with aqueous citric acid solution and extracted 3 times with toluene. The organic layer was mixed and the mixture was washed successively with aqueous ammonium chloride solution and water to give a solution of (2R)-2-(1-ethoxyethoxy)-1-(2,4-difluorophenyl)-1-propanone in toluene. Subsequently, methanol (97 mL) and methanesulfonic acid (0.9 g, 9.4 mmol) were added, and the mixture was stirred at 40° C. for 2.5 hr. The reaction mixture was washed successively with 5% brine (once) and water (two times) and the organic layer was concentrated under reduced pressure to give the title compound as a pale-yellow oil (120 g, yield 69%).

Provenance & Evidence