Methyl formate → 5-Chloro 3-benzyloxy pyridine-4-carboxaldehyde

Participants

Reaction Conditions

Reaction Steps

To a stirred solution of diisopropylamine (4.5 mL, 31.78 mmol) in anhydrous tetrahydrofuran (20 mL) under nitrogen atmosphere at −5° C. was added dropwise n-BuLi in hexanes (2.5 M solution, 12.8 mL, 31.78 mmol) maintaining internal temperature of the reaction mixture below 0° C. The reaction mixture was stirred at −10° C. for 10 minutes, then at 0° C. for 30 minutes. This was cooled to −78° C. and a solution of Example 236A (5.8 g, 26.5 mmol) in anhydrous tetrahydrofuran (30 mL) was added slowly. Stirring at −78° C. was continued for 1 hour. Then the reaction was quenched with dropwise addition of methyl formate (5 mL, 79.5 mmol) in anhydrous THF (15 mL) and stirred at −78° C. for 3.5 hours. Internal temperature of the reaction mixture was maintained at or below −74° C. throughout the reaction. After 3.5 hours, the reaction mixture was poured into an ice cold saturated aqueous solution of NaHCO3 (200 mL) and stirred for 15 minutes. The mixture was partitioned with ethyl acetate (250 mL), organic layer was separated and washed with brine (2×60 mL). The dried (MgSO4) organic layer was concentrated under reduced pressure to obtain the crude product (8.5 g). The title compound was obtained in 75% yield (4.2 g) by flash chromatography on silica gel eluting with 6% acetone-hexane.

Provenance & Evidence