反应详情

(S)-tert-Butyl (1-hydroxypropan-2-yl)carbamate (259 mmol, 45.4 g) and triphenylphosphine (259 mmol, 68.0 g) were mixed in dry EtOAc (380 ml) under nitrogen atmosphere. 2-Chloro-6-fluoro-4-(1H-pyrazol-3-yl)benzonitrile (130 mmol, 35.9 g) was added and the resulting mixture was stirred for 10 min. DIAD (259 mmol, 52.4 g) was added slowly while keeping the temperature between 15-25° C. with an ice bath. After the addition the mixture was allowed to warm to RT and stirred for 4 h. Water and concentrated HCl (1296 mmol, 106 ml) was added to the mixture and stirred for 6 days during which more HCl (107 ml in total) was added. Water and DCM was added and the mixture was stirred for a while before separating the phases. The organic phase was extracted twice with water. The water phases were combined and washed twice with DCM. DCM was added to the water phase and the pH of the water phase was adjusted to 12.5 with 50% NaOH. The phases were separated and the water phase was extracted once more with DCM. The DCM phases were combined and washed once with water. The separated DCM phase was evaporated and dried under vacuum. 24.0 g of the title compound was obtained. 1H-NMR (400 MHz, DMSO-d6): δ 0.96 (d, 3H), 1.18 (bs, 2H), 3.19-3.29 (m, 1H), 3.97-4.08 (m, 2H), 7.03 (d, 1H), 7.85-7.92 (m, 2H), 7.98-8.02 (m, 1H).

1. custombetween 15-25° C.
2. additionAfter the addition the mixture
3. stirringstirred for 4 h
4. additionwas added
5. stirringthe mixture was stirred for a while
6. custombefore separating the phases
7. extractionThe organic phase was extracted twice with water
8. washwashed twice with DCM
9. additionDCM was added to the water phase
10. customThe phases were separated
11. extractionthe water phase was extracted once more with DCM
12. washwashed once with water
13. customThe separated DCM phase was evaporated
14. customdried under vacuum