反应详情

To a solution of 2-(tert-butoxycarbonylamino)-3-fluoro-benzoic acid (37.1 g, 145 mmol), 4-amino-1-benzylpiperidine (35.6 mL, 1.20 equiv.), 1-hydroxybenzotriazole (21.6 g, 1.1 equiv), and triethylamine (44.1 g, 3.0 equiv.) in ethyl acetate (450 mL) was added 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (30.7 g, 1.1 equiv) in one portion. Initially, everything went into solution, but a precipitate formed very rapidly. The reaction was fitted with a reflux condenser and heated at reflux for 5 h. The reaction was diluted with ethyl acetate, washed with water (2×), then 1N sodium hydroxide (2×), then brine, dried over magnesium sulfate, and concentrated to give 67.0 g (quant) as a white solid which was used without purification. 1H-NMR (CDCl3, 500 MHz) δ 1.48 (s, 9H), 1.55 (m, 2H), 1.99 (bd, J=11.0, 2H), 2.17 (dd, J=1.0, 11.0, 2H), 2.84 (bd, J=11.3, 2H), 3.51 (s, 2H), 3.94 (m, 1H), 6.13 (bd, J=7.6, 1H), 7.10-7.28 (m, 4H), 7.31 (m, 4H), 7.59 (s, 1H). Mass spec.: 428.41 (MH)+.

1. customa precipitate formed very rapidly
2. customThe reaction was fitted with a reflux condenser
3. temperatureheated
4. temperatureat reflux for 5 h
5. washwashed with water (2×)
6. dry with material1N sodium hydroxide (2×), then brine, dried over magnesium sulfate
7. concentrationconcentrated
8. customto give 67.0 g (quant) as a white solid which
9. customwas used without purification