(2,2-difluoro-3-phenylmethoxypropyl) methanesulfonate

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A solution of 3-benzyloxy-2,2-difluoropropan-1-ol (Compound 59H, 202 mg, 1 mmol) and methanesulfonyl chloride in DCM (3 mL) was cooled to 0° C. and treated with Et3N (0.28 mL, 2 mmol). The reaction mixture was allowed to warm at RT. After 12 h, the reaction mixture was diluted with DCM (5 mL) and washed with aq. K2CO3 (4×5 mL). The organic layer was dried over Na2SO4, filtered and concentrated to give 220 mg (82%) of the title compound as yellow oil. 1H NMR (500 MHz, CDCl3) δ 7.37-7.33 (m, 5H), 4.62 (s, 2H), 4.47 (t, J=12.4 Hz, 2H), 3.74 (t, J=12.4 Hz, 2H), 3.05 (s, 3H). washed with aq. K2CO3 (4×5 mL) The organic layer was dried over Na2SO4 filtered concentrated

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A cold (0° C.) solution of 4-iodo-1H-pyrazole (10.1 g, 51.8 mmol) in DMF (20 mL) was treated with NaH (1.56 g, 38.82 mmol, 60%) and allowed to warm to RT. After 1 h, the reaction mixture was treated with methanesulfonic acid 3-benzyloxy-2,2-difluoropropyl ester (Compound 59G, 2.0 g, 6.47 mmol) and was stirred for 24 h at 70° C. The reaction mixture was poured into chilled sat. aq. ammonium chloride (20 mL) and extracted with ethyl acetate (100 mL). The organic layer was washed with water (5×30 mL), dried over Na2SO4, filtered, concentrated and purified by column chromatography (SiO2, 30% ethyl acetate/hexanes) to give 1.8 g (72%) of the title compound as a white solid. 1H NMR (500 MHz, CDCl3) δ 7.32-7.38 (m, 7H), 4.63 (s, 2H), 3.89 (s, J=12.5 Hz, 2H), 3.77 (t, J=12.5 Hz, 2H). The reaction mixture was poured extracted with ethyl acetate (100 mL) The organic layer was washed with water (5×30 mL) dried over Na2SO4 filtered concentrated purified by column chromatography (SiO2, 30% ethyl acetate/hexanes)