2,2-二氟-2-苯乙酰基 氯化物

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

实验步骤: To a flask charged with 2,2-difluoro-2-phenylacetic acid (0.8 g, 5.06 mmol), as prepared in the preceding step, under argon in an ice-bath was added oxalyl chloride (5 mL), and the reaction mixture stirred for 15 min. A solution of dimethylformamide (DMF) (37 mg, 0.506 mmol) in DCM (0.5 mL) was added. After 2 hours, the ice-bath was removed, and the mixture continued to stir for 1 hour. The solvents were evaporated, DCM was added, and then evaporated in vacuo giving the title compound (0.88 g, 98% yield), that was used immediately without further purification. as prepared in the preceding step, under argon in an ice-bath After 2 hours the ice-bath was removed to stir for 1 hour The solvents were evaporated DCM was added evaporated in vacuo

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

实验步骤: To a solution of DIEA (1.49 mL, 8.55 mmol) and 2-(3-amino-2-fluoro-6-nitrophenyl)ethyl acetate (690 mg, 2.85 mmol), as prepared in the preceding step, in DCM (6 mL) was added a solution of 2,2-difluoro-2-phenylacetyl chloride (0.99 g, 5.20 mmol), as prepared according to the procedure of step 3 of Example 1, in DCM (3 mL). After stirring for 24 hours, the mixture was concentrated, and partitioned between DCM and H2O. The organic layer was separated, and the aqueous layer extracted with DCM. The organic layers were combined, washed with H2O and brine, dried over Na2SO4, concentrated, and flash chromatographed on silica gel eluting with EtOAc/DCM (0, 2.5, and 5%) to give the title compound (1.04 g, 92% yield) as an orange oil. 1H-NMR (400 MHz, CDCl3) δ 8.49-8.43 (m, 2H), 7.87 (d, J=9.2 Hz, 1H), 6.68 (d, J=7.1 Hz, 2H), 7.55-7.49 (m, 3H), 4.35 (t, J=6.4 Hz, 2H), 3.37 (dt, J=6.3, 2.3 Hz, 2H), 2.01 (s, 3H). as prepared the mixture was concentrated partitioned between DCM and H2O The organic layer was separated the aqueous layer extracted with DCM washed with H2O and brine dried over Na2SO4 concentrated flash chromatographed on silica gel eluting with EtOAc/DCM (0, 2.5, and 5%)

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

实验步骤: To a flask charged with 2,2-difluoro-2-phenylacetic acid (0.8 g, 5.06 mmol), as prepared in the preceding step, under argon in an ice-bath was added oxalyl chloride (5 mL), and the reaction mixture stirred for 15 min. A solution of dimethylformamide (DMF) (37 mg, 0.506 mmol) in DCM (0.5 mL) was added. After 2 hours, the ice-bath was removed, and the mixture continued to stir for 1 hour. The solvents were evaporated, DCM was added, and then evaporated in vacuo giving the title compound (0.88 g, 98% yield), that was used immediately without further purification. as prepared in the preceding step, under argon in an ice-bath After 2 hours the ice-bath was removed to stir for 1 hour The solvents were evaporated DCM was added evaporated in vacuo

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

实验步骤: To a flask charged with 2,2-difluoro-2-phenylacetic acid (0.8 g, 5.06 mmol), as prepared in the preceding step, under argon in an ice-bath was added oxalyl chloride (5 mL), and the reaction mixture stirred for 15 min. A solution of dimethylformamide (DMF) (37 mg, 0.506 mmol) in DCM (0.5 mL) was added. After 2 hours, the ice-bath was removed, and the mixture continued to stir for 1 hour. The solvents were evaporated, DCM was added, and then evaporated in vacuo giving the title compound (0.88 g, 98% yield), that was used immediately without further purification. as prepared in the preceding step, under argon in an ice-bath After 2 hours the ice-bath was removed to stir for 1 hour The solvents were evaporated DCM was added evaporated in vacuo