Toluene → 7-(5-Chloro-2-fluorophenyl)-4-methyl-5,6,7,8-tetrahydroquinolin-5-one hydrochloride

To a mixture of 1-amino-5-(5-chloro-2-fluorophenyl)cyclohexan-3-one (1.33 g), 1,1-dimethoxy-3-butanone (2 ml), toluene (20 ml) and ethanol (9 ml) was added granulated potassium hydroxide (0.4 g) at 110-115° C. while stirring. Just after potassium hydroxide was dissolved, granulated potassium hydroxide (0.3 g) was added to the mixture. With 30 minutes intervals, granulated potassium hydroxide (0.1 g) was added three times to the mixture. To the mixture was added 1,1-dimethoxy-3-butanone (1ml) 2 hours after the reaction had started, and then granulated potassium hydroxide (0.1 g) was added to the mixture. The mixture was stirred for 1 hour under the same conditions. The reaction solution was concentrated under reduced pressure, and to the residue was added water (30 ml) and ethyl acetate (100 ml). The mixture was shaken and the separated upper layer was washed with water. To the mixture was added concentrated hydrochloric acid (0.5 ml). The mixture was concentrated under reduced pressure, and the residue washed with a little amount of ethanol and dried to give 7-(5-chloro-2-fluorophenyl)-4-methyl-5,6,7,8-tetrahydroquinolin-5-one hydrochloride (1.05 g).

1. stirringThe mixture was stirred for 1 hour under the same conditions
2. concentrationThe reaction solution was concentrated under reduced pressure
3. additionto the residue was added water (30 ml) and ethyl acetate (100 ml)
4. stirringThe mixture was shaken
5. washthe separated upper layer was washed with water
6. additionTo the mixture was added concentrated hydrochloric acid (0.5 ml)
7. concentrationThe mixture was concentrated under reduced pressure
8. washthe residue washed with a little amount of ethanol
9. customdried

ORD record

ord-67de1ded8331485899e79d680960fbde

Source dataset

uspto-grants-2002_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06350749B1