反应详情

Acetyl chloride (7.7 ml, 108 mmol) was added over a period of 45 minutes to a solution of 3-(trifluoromethyl)-1H-pyrazol-5-amine (6.5 g, 43 mmol) and N-methylmorpholine (12.3 ml, 112 mmol) in CH2Cl2 (160 ml) with cooling in an ice bath. The reaction was allowed to warm to room temperature and stirred for 16 h, the solvent was removed in vacuo and the residue dissolved in methanol (150 ml). The solution was cooled in an ice bath and 25% aqueous NaOH (7.3 ml, 65 mmol) was added. After 3.25 h, 25% aqueous NaOH (0.5 ml, 4.4 mmol) was added and the reaction stirred for an additional 1.5 h. 2N HCl (20 ml) was added and the organic solvents were removed in vacuo at below 35° C. Water was added and the crude then extracted EtOAc (×2) and the extracts dried (MgSO4) and concentrated in vacuo. The resultant residue was suspended in CH2Cl2 (20 ml) with stirring. The solid was filtered and washed with CH2Cl2 (2×3 ml) and dried in vacuo to provide the title compound as a white solid (7.3 g) which was used in the subsequent step.

1. temperaturewith cooling in an ice bath
2. customthe solvent was removed in vacuo
3. dissolutionthe residue dissolved in methanol (150 ml)
4. temperatureThe solution was cooled in an ice bath
5. waitAfter 3.25 h
6. stirringthe reaction stirred for an additional 1.5 h
7. customthe organic solvents were removed in vacuo at below 35° C
8. additionWater was added
9. dry with materialthe crude then extracted EtOAc (×2) and the extracts dried (MgSO4)
10. concentrationconcentrated in vacuo
11. stirringwith stirring
12. filtrationThe solid was filtered
13. washwashed with CH2Cl2 (2×3 ml)
14. customdried in vacuo