反应详情

To a suspension of 24.7 g (87 mmol) of (3-{[(benzyloxy)carbonyl]amino}phenyl)acetic acid in 200 mL of dichloromethane (from Step B) was added triethylamine (30.2 mL, 173 mmol) which resulted in some exotherming (+5° C.) and the suspension becoming a solution. After 10 min cooling, HOBt (13.2 g, 87 mmol), N,O-dimethylhydroxylamine HCl (8.5 g, 87 mmol) was added to the solution followed by EDC (16.6 g, 87 mmol) and the resulting mixture stirred at room temperature overnight under nitrogen atmosphere. The solution was transferred to a separatory funnel and washed with 1 M HCl which caused an emulsion. Methanol was added to break up the emulsion and the aqueous was partitioned off. The organics were dried over sodium sulfate, filtered and concentrated under vacuum. Recrystallization of the residue from 1000 mL of 70% hexane in ethyl acetate (heated to reflux and then cooled to room temperature overnight) afforded the title compound (21 g, 74%) as a white solid. LC-MS: m/z (ES) 329 (MH)+.

1. customresulted in some exotherming (+5° C.)
2. temperatureAfter 10 min cooling
3. customThe solution was transferred to a separatory funnel
4. washwashed with 1 M HCl which
5. additionMethanol was added
6. customthe aqueous was partitioned off
7. dry with materialThe organics were dried over sodium sulfate
8. filtrationfiltered
9. concentrationconcentrated under vacuum
10. customRecrystallization of the residue from 1000 mL of 70% hexane in ethyl acetate (
11. temperatureheated
12. temperatureto reflux
13. temperaturecooled to room temperature overnight)