Hydrochloric Acid → (2,4-Difluoro-3-formyl-phenyl)-carbamic acid tert-butyl ester

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Reaction Conditions

Reaction Steps

To a stirred, cooled (−78° C.) solution of (2,4-difluoro-phenyl)-carbamic acid tert-butyl ester (5 g) in THF (50 ml) under an argon atmosphere was added dropwise a 1.6 M solution of BuLi in hexanes (28.6 ml) for 20 min (temperature below −68° C. during the addition). When addition was complete, the mixture (turning to orange, then to light red) was stirred at −78° C. for 1 h 30. DMF (7.55 ml) was then added for 10 min (temperature below −70° C.) and stirring at −78° C. was continued for 15 min. As the mixture had turned to a compact mas (no more stirring), it was allowed to warm to room temperature. Water (50 ml) was added and the pH was set to 3 by the dropwise addition of 3 N HCl. EtOAc (50 ml) was added. The organic phase was washed with water and brine dried over MgSO4, filtered and concentrated. The crude product was purified by flash chromatography (cyclohexane=>cyclohexane/EtOAc 85:15) to give (2,4-difluoro-3-formyl-phenyl)-carbamic acid tert-butyl ester (1.75 g) as an off-white solid.

Provenance & Evidence