tert-Butyl methyl ether → N-[(3R,4S)-6-Bromo-3-hydroxy-chroman-4-yl]-4-fluoro-benzamide

참여 물질

반응 단계

To a suspension of (3R,4S)-4-amino-6-bromo-chroman-3-ol (692 g, 2.84) and sodium bicarbonate (476 g, 5.67 mol) in tetrahydrofuran (3.0 L) and water (3.0 L) at 17° C. add 4-fluorobenzoyl chloride (369 mL, 3.12 mol) dropwise via addition funnel over 15 min. and stir for 2 hr. Add water (2 L) and methyl tert-butyl ether (3.5 L) and stir for 5 min. Separate the organic phase and wash it with water (2 L) and brine (2 L). Dry the organic portion over anhydrous magnesium sulfate and concentrate in vacuo to obtain a pale yellow solid (2.3 kg). Triturate the solid in heptane (5 L) at 25° C. for 3 h. Collect by filtration and dry in an oven at 50° C. for 12 hr. to obtain the title compound (975 g, 94%) as a white solid. LC-ES/MS m/z (79Br/81Br) 366/368 [M+H]+.

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