2,2-difluoro-3-phenylmethoxypropan-1-ol

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

Procedure: A suspension of 2,2-difluoropropane-1,3-diol (Compound 59I, 6.0 g, 53.5 mmol), 4-fluorophenylboronic acid (1.5 g, 10.7 mmol) and K2CO3 (11.0 g, 80.3 mmol) in DMF (50 mL) was treated with benzyl bromide (8.9 mL, 74.9 mmol). The reaction mixture was stirred at RT for 72 h, diluted with ethyl acetate (200 mL) and washed with water (5×100 mL). The organic layer was dried over Na2SO4, filtered and concentrated to give yellow oil which was purified by column chromatography (SiO2, 20% ethyl acetate/hexanes) to give 5 g (50%) of the desired product as an oil. 1H NMR (500 MHz, CDCl3) δ 7.38-7.34 (m, 5H), 4.70 (s, 2H), 3.89-3.88 (m, 2H), 3.77 (t, J=12.6 Hz, 2H). washed with water (5×100 mL) The organic layer was dried over Na2SO4 filtered concentrated to give yellow oil which was purified by column chromatography (SiO2, 20% ethyl acetate/hexanes)

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