4-Bromoanisole → HCID 57978150, compound

Participants

Reaction Steps

Butyllithium (2.5 M in hexanes, 0.947 mL) was added dropwise to a solution of 4-bromoanisole (483 mg, 2.58 mmol) in anhydrous THF at −78° C. under an atmosphere of argon. The mixture was stirred at that temperature for 30 min and then a solution of N-[(1E)-(3-bromophenyl)(2-cyanopyridin-3 -yl)methylene]-2-methypropane-2-sulfinamide (Example 2, 840 mg, 2.15 mmol) in THF (10 mL) was added dropwise. Stirring was continued for 3 h at −78° C., and then for 1 h at −25° C. The reaction was quenched by the addition of water, the mixture was diluted with ethyl acetate and washed with water, dried over magnesium sulfate and concentrated. The residue was dissolved in methanol (20 mL) and to this was added 2 M hydrochloric acid in diethyl ether (2.5 mL). The mixture was stirred at room temperature for 22 h and then concentrated. The residue was partitioned between dichloromethane and saturated aqueous sodium hydrogen carbonate, dried over sodium sulfate and concentrated. Purification by column chromatography using a gradient of increasing concentration of ethyl acetate in dichloromethane (0-50%) and finally 5% of 2 M ammonia in methanol in ethyl acetate-dichloromethane (45:50) gave 115 mg (14% yield) of the title compound. 1H NMR (CDCl3) δ 8.62 (dd, 1H), 7.88 (dd, 1H), 7.46 (t, 1H), 7.37 (m, 2H), 7.26 (m, 1H), 7.21 (m, 2H), 7.14 (t, 1H), 6.81 (m, 2H), 3.78 (s, 3H); MS (ESI) m/z 394, 396 [M+1]+.

Provenance & Evidence