2,2-二氯乙腈

反应条件: temp:0.00; pressure:0.00; stir:

反应条件: temp:-40.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: Under an atmosphere of nitrogen, 3-benzyloxypropyl-magnesium chloride is prepared from 1-chloro-3-benzyloxypropane (2.42 g, 13 mmol) in dry ether (13 ml) and magnesium turnings (660 mg, 26 mmol). The Grignard solution is separated from the excess of magnesium, cooled to -40° C., and a 10% solution of difluoroacetonitrile in dry THF (10 ml, 13 mmol) is added dropwise, maintaining the temperature at -40° C. After stirring at this temperature, for 30 minutes, the mixture is poured into a cold (0° C.) solution of sodium cyanide (1.27 g) and ammonium chloride (2.10 g) in water (40 ml). The mixture is stirred vigorously for 1 hour; during that time the reaction is allowed to warm up to room temperature. The organic phase is separated and extracted with 2 N HCl. Basification with concentrated ammonia (pH ~9-10), extraction with ether, drying, and evaporation gives the title compound as an oil (1.5 g). The Grignard solution is separated from the excess of magnesium maintaining the temperature at -40° C The mixture is stirred vigorously for 1 hour to warm up to room temperature The organic phase is separated extracted with 2 N HCl Basification with concentrated ammonia (pH ~9-10), extraction with ether drying evaporation

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To a cooled (0° C.) solution of sodium methoxide (25 wt % solution in methanol; 0.230 mL, 1.032 mmol) and MeOH (20 mL) was added dropwise difluoroacetonitrile (0.690 mL, 10.03 mmol) while maintaining an internal temperature of <1° C. After 20 min DL-serine methyl ester hydrochloride (1.55 g, 9.96 mmol) was added followed by MeOH (20 mL) and the reaction was allowed to warm to rt overnight. Subsequently, the reaction was heated to 55° C. for 5 h. The reaction was cooled to rt and partitioned between DCM/water. The aqueous layer was extracted with DCM (3×) and the combined organic layers were washed with water and dried over MgSO4. The filtrate was concentrated in vacuo to give 1.59 g (89%) of a light-brown oil. MS m/z=180 [M+H]+. Calculated for C6H7F2NO3:179. while maintaining an internal temperature of <1° C Subsequently, the reaction was heated to 55° C. for 5 h The reaction was cooled to rt partitioned between DCM/water The aqueous layer was extracted with DCM (3×) the combined organic layers were washed with water dried over MgSO4 The filtrate was concentrated in vacuo