反应详情

A mixture of 2-chloro-4-fluoro-3-methyl-benzonitrile (500 mg, 2.95 mmol), diisopropylethylamine (1.29 mL, 7.37 mmol), and (1S,2R)-2-aminocyclohexanol hydrochloride (670 mg, 4.42 mmol, Acros®) is microwaved using a CEM® microwave at 190° C. for 2 h and 180° C. for 4 h. The mixture is diluted with dichloromethane and washed with 1 N HCl. The aqueous layer is extracted again with dichloromethane. The combined organic phases are dried over sodium sulfate, filtered, and concentrated in vacuo. The resulting residue is purified using radial chromatography, eluting with 2% methanol/dichloromethane. The isolated product is recrystallized with ether and hexane to yield the title compound as a white solid (231 mg, 29%). LC-ES/MS m/z 265.0 (M+1).

1. customis microwaved
2. customat 190° C.
3. customfor 2 h
4. washwashed with 1 N HCl
5. extractionThe aqueous layer is extracted again with dichloromethane
6. dry with materialThe combined organic phases are dried over sodium sulfate
7. filtrationfiltered
8. concentrationconcentrated in vacuo
9. customThe resulting residue is purified
10. washeluting with 2% methanol/dichloromethane
11. customThe isolated product is recrystallized with ether and hexane