反应详情

温度

57.5 °C

To a reactor containing tert-butyl 2-(1,1,1-trifluorobut-3-en-2-yloxy)acetate (1.150 kg, 4.788 mol) was added formic acid (6.2 kg) at rt. The reaction mixture was heated to 55-60° C. for 4-5 h. The formic acid was evaporated under vacuum (T=40-45° C.) and chased with toluene (2×3.0 L). To the residue was added CH2Cl2 (2.0 L) and further concentrated under vacuum. To the resulting residue was added CH2Cl2 (4.6 L) and the solution was cooled to 0° C., followed by N,N-carbonyldiimidazole (1.05 kg, 6.49 mol) in five portions. The mixture was stirred for 30 mins, and N,O-dimethylhydroxylamine hydrochloride (0.67 kg, 6.72 mol) was added in portions while maintaining temperature below 10° C. The reaction mixture was warmed to rt and stirred over 14 h. The reaction mixture was cooled to 3.2° C. and imidazole (100.7 g, 1.48 mol) was charged in two portions. The reaction mixture was warmed to rt and water (1.4 kg) was added, followed by methyl tert-butyl ether (14.0 L). The organic phase was washed with 2.0 N aq. HCl (1.0 L and 0.7 L), followed by sat. aq. NaHCO3 (1.2 L) and sat. aq. NaCl (1.20 L). The organics were concentrated to afford the title compound as an oil (0.95 kg, 87.2%). 1H NMR (500 MHz, CDCl3) δ ppm 5.85-5.76 (m, 1H), 5.62 (d, J=17.2 Hz, 1H), 5.56 (d, J=10.4 Hz, 1H), 4.49-4.34 (m, 3H), 3.68 (s, 3H), 3.67 (s, 1H), 3.18 (s, 3H), 3.08 (s, 1H); 13C NMR (126 MHz, cdcl3) δ ppm 169.9*, 163.4*, 128.61, 123.87 (d, J=282.0 Hz), 123.82, 78.54 (q, J=31.3 Hz), 66.12, 61.52, 60.56, 36.20, 32.24. Note: this compound is a 3:1 mixture of amide bond rotamers. *Carbonyl chemical shifts estimated indirectly through 1H-13C HMBC (heteronuclear multiple-bond correlation).

1. customThe formic acid was evaporated under vacuum (T=40-45° C.) and chased with toluene (2×3.0 L)
2. additionTo the residue was added CH2Cl2 (2.0 L)
3. concentrationfurther concentrated under vacuum
4. additionTo the resulting residue was added CH2Cl2 (4.6 L)
5. temperaturethe solution was cooled to 0° C.
6. temperaturewhile maintaining temperature below 10° C
7. temperatureThe reaction mixture was warmed to rt
8. stirringstirred over 14 h
9. temperatureThe reaction mixture was cooled to 3.2° C.
10. temperatureThe reaction mixture was warmed to rt
11. washThe organic phase was washed with 2.0 N aq. HCl (1.0 L and 0.7 L)
12. concentrationThe organics were concentrated