5-bromo-2-(diethoxymethyl)-1,3-difluorobenzene

Conditions: temp:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 5-bromo-2-(diethoxymethyl)-1,3-difluorobenzene (14.7 g, 0.05 mol) in t-butylmethylether (290 mL) was added n-BuLi (21 mL of 2.5 M in hexanes, 0.052 mol) at −78° C. under argon. The reaction was then stirred at −78° C. for 1 hour. Acetone (4.9 mL, 0.065 mol) was added dropwise to the reaction mixture. The reaction solution was then slowly warmed to 0° C. and stirred for 30 min. The reaction was quenched with saturated aqueous sodium bicarbonate. The mixture was extracted with ethyl acetate. The organic phase was dried and concentrated to afford the title compound. No further purification was performed. 1H NMR (300 MHz, CDCl3): δ 10.34 (s, 1H), 87.03 (d, 2H), 5.74 (s, 1H), 3.85-3.71 (m, 2H), 3.60 (q, 2H), 1.52 (s, 6H), 1.24 (t, 6H). The reaction solution was then slowly warmed to 0° C. stirred for 30 min The reaction was quenched with saturated aqueous sodium bicarbonate The mixture was extracted with ethyl acetate The organic phase was dried concentrated

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

Procedure: 4-Bromo-2,6-difluorobenzaldehyde (22 g, 0.1 mol) was dissolved in ethanol (46 g, 1 mol). Methyl orthoformate (17.76 g, 0.12 mol) and PPTS (2.52 g, 0.01 mol) were added, and then the mixture was heated to reflux for 7 hours. Upon completion, the reaction mixture was directly concentrated in vacuo. The resulting oily solid was taken up in ethyl acetate and washed with saturated aqueous sodium bicarbonate. The organic layer was dried over anhydrous magnesium sulfate, filtered and concentrated in vacuo to afford the title compound. No further purification was performed. 1H NMR (300 MHz, CDCl3): δ 7.00 (d, 2H), 5.60 (s, 1H), 3.68 (q, 2H), 3.49 (q, 2H), 1.17 (t, 6H). the mixture was heated to reflux for 7 hours Upon completion, the reaction mixture was directly concentrated in vacuo washed with saturated aqueous sodium bicarbonate The organic layer was dried over anhydrous magnesium sulfate filtered concentrated in vacuo