Chloroacetyl chloride → (R)-5-isopropylmorpholin-3-one

Participants

Reaction Conditions

Reaction Steps

NaH (6.24 g, 60% wt in mineral oil, 156 mmol, 2.3 equiv) was charged into a 1 L RB flask, followed by addition of 100 mL of toluene. The suspension was stirred in an ice bath. (2R)-2-Amino-3-methyl-1-butanol (7.0 g, 67.9 mmol) in 50 mL of toluene was added portion-wise. Addition took 10 minutes, followed with removal of the cooling bath. The mixture was stirred at ambient temperature for 15 minutes, and cooled in an ice bath. To the cooled mixture was added portion-wise a solution of chloroacetyl chloride (6.25 mL, 78 mmol, 1.15 equiv) in 50 mL of toluene. The mixture began to foam. When the addition neared completion, foaming subsided. The resulting mixture was heated under a reflux condenser to 90° C. (oil bath temp) for 20 hours. The mixture was cooled to room temperature, followed by addition of 22 g of NH4Cl and then water (50 mL). The phases were separated. The aqueous phase was extracted with EtOAc (2×150 mL). The combined organic was dried over Na2SO4, filtered and concentrated in vacuo. The residue was triturated in 30 mL of hexane. The solids formed were collected by filtration, washing with hexane (2×10 mL). Drying under vacuum at room temperature for 5 hours gave the title compound (6.53 g) as a cream-colored solid. LC-MS (ES) m/z=144

Provenance & Evidence