反应详情

2-chloro-6-fluoro-4-(1H-pyrazol-3-yl)benzonitrile (5.0 g, 22.56 mmol), N-t-BOC-(R)-1-amino-2-propanol (7.91 g, 45.1 mmol) and triphenylphosphine (11.84 g, 45.1 mmol) were dissolved in dry ethyl acetate under nitrogen atmosphere and stirred. DIAD (9.12 g, 45.1 mmol) was added dropwise and the reaction flask was cooled by ice bath. The reaction was stirred at RT overnight. Water and concentrated HCl (18.53 ml, 226 mmol) were added to the reaction mixture and the reaction was stirred at RT overnight. Water and DCM were added to the reaction mixture, stirred and water phase was separated. Organic phase was extracted twice with water and water phases were combined. The combined water phase was washed twice with DCM and pH of water was adjusted to ˜12 by addition of NaOH. Water phase was extracted twice with DCM and combined DCM phase was washed twice with water. Organic phase was evaporated to dryness and the product was purified by Flash-chromatography. Yield 31.8%. 1H-NMR (400 MHz; DMSO): δ 1.42 (d, 3H), 2.80-3.00 (m, 2H), 4.27-4.38 (m, 1H), 7.03 (d, 1H), 7.84-7.95 (m, 2H), 8.00 (m, 1H).

1. temperaturethe reaction flask was cooled by ice bath
2. stirringThe reaction was stirred at RT overnight
3. stirringthe reaction was stirred at RT overnight
4. stirringstirred
5. customwater phase was separated
6. extractionOrganic phase was extracted twice with water and water phases
7. washThe combined water phase was washed twice with DCM and pH of water
8. additionwas adjusted to ˜12 by addition of NaOH
9. extractionWater phase was extracted twice with DCM and combined DCM phase
10. washwas washed twice with water
11. customOrganic phase was evaporated to dryness
12. customthe product was purified by Flash-chromatography