[4-(3-bromophenyl)-3,6-dihydro-2H-pyran-3-yl]methanol

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

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

Procedure: A 0° C. solution of (4-(3-bromophenyl)-3,6-dihydro-2H-pyran-3-yl)methanol (0.305 g, 1.08 mmol) in CH2Cl2 (10 mL) is treated with triethylamine (0.218 g, 2.15 mmol) and then methanesulfonyl chloride (0.148 g, 1.29 mmol) and the reaction is stirred at 0° C. for 30 min. The reaction is diluted with water and extracted with CH2Cl2. The organic layer is dried over Na2SO4 and the solvent is removed under reduced pressure to afford the title compound (0.432 g, 97%). 1H NMR (400 MHz, CDCl3) δ 7.51 (t, J=1.8 Hz, 1H), 7.44-7.41 (m, 1H), 7.31-7.29 (m, 1H), 7.25-7.21 (m, 1H), 6.18 (t, J=2.6 Hz, 1H), 4.33-4.31 (m, 2H), 4.20 (dd, J=1.5, 11.6 Hz, 2H), 4.14-4.08 (m, 1H), 3.72-3.68 (m, 1H), 3.01-2.98 (m, 1H), 2.95 (s, 3H). extracted with CH2Cl2 The organic layer is dried over Na2SO4 the solvent is removed under reduced pressure

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A 0° C. solution of 4-(3-bromophenyl)-3,6-dihydro-2H-pyran (0.50 g, 2.09 mmol) in CH2Cl2 (15 mL) is treated with paraformaldehyde (0.208 g, 2.20 mmol) and stirred for 5 minutes at 0° C. A 1 M solution of dimethylaluminum chloride in hexanes (3.03 mL, 3.03 mmol) is added drop-wise to the slurry. The reaction is warmed to room temperature and stirred for 1 hour. The reaction is cooled to 0° C. and more paraformaldehyde (0.208 g, 2.20 mmol) and 1 M solution of dimethylaluminum chloride in hexanes (3.03 mL, 3.03 mmol) is added. The reaction is warmed to room temperature and stirred overnight. The reaction is quenched by pouring into an ice/1 N HCl mixture and is extracted three times with EtOAc. The combined organic layers are dried over Na2SO4 and the solvent is removed under reduced pressure to afford a residue that is purified on silica gel chromatography eluting with a linear gradient of 5% to 100% EtOAc in hexanes to give the title compound (0.315 g, 53%). 1H NMR (400 MHz, CDCl3) δ 7.50 (t, J=2.0 Hz, 1H), 7.40 (dd, J=2.2, 7.9 Hz, 1H), 7.29-7.27 (m, 1H), 7.20 (t, J=7.9 Hz, 1H), 6.11 (t, J=2.9 Hz, 1H), 4.32-4.29 (m, 2H), 4.28-4.25 (m, 1H), 3.76 (dd, J=3.1, 11.4 Hz, 1H), 3.70-3.64 (m, 2H), 2.70 (d, J=2.2 Hz, 1H), 1.89 (dd, J=4.6, 6.4 Hz, 1H). The reaction is warmed to room temperature stirred for 1 hour The reaction is cooled to 0° C. The reaction is warmed to room temperature stirred overnight The reaction is quenched by pouring into an ice/1 N HCl mixture is extracted three times with EtOAc The combined organic layers are dried over Na2SO4 the solvent is removed under reduced pressure to afford a residue that is purified on silica gel chromatography eluting with a linear gradient of 5% to 100% EtOAc in hexanes