2-chloro-6-fluoro-4-methylbenzaldehyde

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

Procedure: Sodium borohydride (1.42 g, 37.5 mmol) was added in portions to an ice-cooled solution of 2-chloro-6-fluoro-4-methylbenzaldehyde (6.25 g, 38.2 mmol) in methanol (56 mL); once addition was complete the reaction was allowed to warm rt with stirring over 1 h and then concentrated in vacuo. The residue was partitioned between ether and saturated aqueous sodium bicarbonate solution. The layers were separated and the aqueous re-extracted with ether. The organic layers were combined, washed with H2O, dried with MgSO4 and concentrated in vacuo to yield the crude product as an oil. This oil was diluted with pentane, cooled and stirred which resulted in a white solid. Filtration and drying in vacuo yielded the title compound (5.10 g, 29.2 mmol). once addition concentrated in vacuo The residue was partitioned between ether and saturated aqueous sodium bicarbonate solution The layers were separated the aqueous re-extracted with ether washed with H2O dried with MgSO4 concentrated in vacuo to yield the crude product as an oil cooled stirred which resulted in a white solid Filtration drying in vacuo

Conditions: temp:-70.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Under Ar, a 2.5M solution of n-BuLi (6.0 mL, 15.0 mmol) was added slowly to a solution of 3-chloro-5-fluorotoluene (2.0, 13.8 mmol) in THF (20 mL) cooled in a dry ice/acetone bath at approximately −70° C. After the addition was complete, the reaction was stirred for 1 h at approximately −70° C. and a solution of N-formylmorpholine (2.3 g, 2.0 mmol) in THF (10 mL) was added dropwise. After stirring for 10 min, the reaction was allowed to warm to rt with stirring over 1 h, then cooled to −30° C. and quenched by the addition of H2O then 1M citric acid. The mixture was allowed to warm to rt with stirring and the phases were separated. The aqueous phase was extracted with EtOAc and the combined organic phases were washed with H2O, dried with MgSO4 and concentrated to yield the title compound as an oil which solidified on standing (2.2 g, 12.8 mmol). After the addition After stirring for 10 min to warm to rt with stirring over 1 h cooled to −30° C. quenched by the addition of H2O to warm to rt with stirring the phases were separated The aqueous phase was extracted with EtOAc the combined organic phases were washed with H2O dried with MgSO4 concentrated