反应详情

To a mixture of methyl 3-amino-4-formylbenzoate (110 mg, 0.614 mmol) in 6 mL THF plus 4 mL saturated NaHCO3 and 1 mL H2O at rt was added ethyl chloroformate (0.070 mL, 0.737 mmol) at the reaction stirred at rt. After 50 min, an additional 0.5 mL saturated NaHCO3 and 5 drops ethyl chloroformate was added. At 17.5 hours the mixture was heated to 60° C., 1 mL saturated Na2CO3 added, and 5 drops ethyl chloroformate added. Then to push reaction to completion, a small scoop of solid Na2CO3 was added and additional ethyl chloroformate added drop-wise until the reaction was approximately 80% complete (45 hours total reaction time). The reaction was partitioned between EtOAc and aqueous NaHCO3 solution, the EtOAc layer washed with brine, dried with Na2SO4, and evaporated. The solid was crystallized from hexane/EtOAc and the filtrate chromatographed eluting with 2.5% MeOH/CHCl3. The impure products from crystallization and chromatography were combined and then recrystallized from hexane/EtOAc to give the title compound as a light yellow solid (63.8 mg, 41%). 1H NMR (CDCl3) δ: 10.53 (br. s, 1H), 10.00 (d, J=0.6 Hz, 1H), 9.11-9.12 (m, 1H), 7.80-7.84 (m, 1H), 7.72-7.76 (m, 1H), 4.28 (q, J=7.2 Hz, 2H), 3.95 (s, 3H), 1.35 (t, J=7.2 Hz, 3H).

1. temperatureAt 17.5 hours the mixture was heated to 60° C.
2. customreaction to completion
3. customapproximately 80% complete (45 hours total reaction time)
4. customThe reaction was partitioned between EtOAc and aqueous NaHCO3 solution
5. washthe EtOAc layer washed with brine
6. dry with materialdried with Na2SO4
7. customevaporated
8. customThe solid was crystallized from hexane/EtOAc
9. customthe filtrate chromatographed
10. washeluting with 2.5% MeOH/CHCl3
11. customThe impure products from crystallization and chromatography
12. customrecrystallized from hexane/EtOAc