反应详情

A solution of 2-chloro-4-nitrobenzoic acid (10.0 g, 49.6 mmoles), (L)-glutamate diethyl ester hydrochloride (11.9 g, 49.6 mmoles), and 1-hydroxybenzotriazole (6.7 g, 49.6 mmoles) in dry dimethylformamide (2150 mL) was stirred under nitrogen while triethylamine (5.02 g, 6.92 mL, 49.6 mmoles) was added dropwise during 1 minute. After 15 minutes, 1,3-dicyclohexylcarbodiimide (11.3 g, 54.6 mmoles) was added in portions during 1 minute. The reaction mixture was filtered after 18 hours and the solids were rinsed with dichloromethane (2×50 mL). The filtrate was spin evaporated (high vacuum) to an amber residue that was dissolved in dichloromethane (300 mL). The organic phase was washed successively with saturated bicarbonate, 5% citric acid, and brine solution (1×300 mL each). The organic phase was then dried (MgSO4), filtered, and poured onto a silica gel column (500 g, pre-wet with dichloromethane). The column was rinsed with dichloromethane (500 mL), followed by gradient elution of the product with 10% and 15% added ethyl acetate (8×250 mL fractions each). Like fractions were combined by spin evaporation and dried to give a white solid; yield, 9.8 g (51%); mp 95°-96° C.; 1H-NMR (DMSO-d6) δ 1.17 and 1.21 (2t overlapped, 6H), 1.8-2.2 (m, 2H), 2.46 (t obscured by DMSO, 2H), 4.0-4.2 (2 q overlapped, 4H), 4.46 (m, 1H), 7.68 (d, Jo =8 Hz, 1H), 8.25 (dxd, Jo =8 Hz, Jm =2 Hz, 1H), 8.34 (d, Jm 2 Hz, 1H), 9.14 (d, 1H); uv (MeOH) 260 nm max (9930), 236 min (6180), 205 max (25600); mass spec (CI) m/e 387 (100%), 341 (40), 184 (21).

1. additionwas added dropwise during 1 minute
2. filtrationThe reaction mixture was filtered after 18 hours
3. washthe solids were rinsed with dichloromethane (2×50 mL)
4. customevaporated (high vacuum) to an amber residue that
5. dissolutionwas dissolved in dichloromethane (300 mL)
6. washThe organic phase was washed successively with saturated bicarbonate, 5% citric acid, and brine solution (1×300 mL each)
7. dry with materialThe organic phase was then dried (MgSO4)
8. filtrationfiltered
9. additionpoured onto a silica gel column (500 g, pre-wet with dichloromethane)
10. washThe column was rinsed with dichloromethane (500 mL)
11. washfollowed by gradient elution of the product with 10% and 15%
12. additionadded ethyl acetate (8×250 mL fractions each)
13. customLike fractions were combined by spin evaporation
14. customdried
15. customto give a white solid
16. customyield