反应详情

A solution of 2-fluoro-4-nitrobenzoic acid (6.26 g, 33.8 mmoles), (L)-glutamate di-tert-butyl ester hydrochloride (10.0 g, 33.8 mmoles), and 1-hydroxybenzotriazole (4.57 g, 33.8 mmoles) in dry dimethylformamide (150 mL) was stirred under nitrogen while triethylamine (3.42 g, 4.71 mL, 33.8 mmoles) was added in one portion. After 15 minutes, 1.3-dicyclohexylcarbodiimide (7.67 g, 37.2 mmoles) was added in portions during 1 minute. The reaction mixture was filtered after 20 hours and the solids rinsed with dichloromethane (1×50 mL). The filtrate was spin evaporated to an amber residue that was partitioned between dichloromethane and saturated bicarbonate solution (200 mL each). The organic phase was washed successively with saturated bicarbonate, 5% citric acid, and brine (1×200 mL each). The organic phase was then dried (MgSO4), filtered, spin evaporated, and dried (high vacuum) to an oily yellow solid (11.9 g, 83%) that showed a major spot on tlc (silica, 2:1 hexane/ethyl acetate, Rf =0.5). The product was purified by the flash chromatography technique to give a light green gum; yield, 9.7 g (67%); 1H-NMR (CDCl3) δ 1.42 (s, 9H), 1.50 (s, 9H), 2.02-2.41 (m, 4H), 4.72 (m, 1H), 7.44 (br t, 1H), 8.0-8.3 (m, 3H); uv (MeOH) 260 nm max (11000), 225 min (4710), 215 sh (7680); mass spec (CI) m/e 427 (24%), 371 (20), 315 (100).

1. additionwas added in one portion
2. filtrationThe reaction mixture was filtered after 20 hours
3. washthe solids rinsed with dichloromethane (1×50 mL)
4. customevaporated to an amber residue that
5. customwas partitioned between dichloromethane and saturated bicarbonate solution (200 mL each)
6. washThe organic phase was washed successively with saturated bicarbonate, 5% citric acid, and brine (1×200 mL each)
7. dry with materialThe organic phase was then dried (MgSO4)
8. filtrationfiltered
9. customspin evaporated
10. dry with materialdried (high vacuum) to an oily yellow solid (11.9 g, 83%) that
11. customThe product was purified by the flash chromatography technique
12. customto give a light green gum
13. customyield