Lithium Hexamethyldisilazide → HCID 66653220, compound

Participants

Reaction Conditions

Reaction Steps

N-(2,4-Dimethoxybenzyl)-5-fluoropyrimidin-2-amine (Preparation 18, 4.00 g, 15.2 mmol) was dissolved in tetrahydrofuran (40 mL) and cooled to −78° C. A 1.0 M solution of lithium hexamethyldisilazide in tetrahydrofuran (17 mL, 17 mmol) was added drop-wise to the solution and the solution was stirred for 30 minutes at −78° C. A solution of 5-chloro-2,4-difluorobenzenesulfonyl chloride (3.42 g, 13.8 mmol) in tetrahydrofuran was added drop-wise to the reaction mixture and it was stirred at −78° C. for 1 h then allowed to warm gradually to ambient temperature. The reaction mixture was stirred for 16 hours then quenched with saturated aqueous ammonium chloride (50 mL). The aqueous phase was extracted with ethyl acetate (×2). The combined organic phase was washed with brine, dried over anhydrous magnesium sulfate, filtered and concentrated in vacuo. The residue was adsorbed onto diatomaceous earth and purified by silica gel column chromatography (hexanes to dichloromethane gradient elution) to afford the title compound as a white solid (1.73 g).

Provenance & Evidence