Acetic Acid → 4-Chloro-2-[(3-hydroxy-1-phenylpropyl)methylamino]benzonitrile

To a stirred suspension of sodium hydride (60% dispersion, 270 mg, 6.75 mmol) in dry tetrahydrofuran (20 ml) under nitrogen and at 0° C. was added 4-chloro-2-[[3-[[(1,1-dimethylethyl)dimethylsilyl]oxy]-1-phenylpropyl]amino]benzonitrile (2.3 g, 5.74 mmol) in tetrahydrofuran (10 ml). The resulting yellow suspension was stirred at room temperature for 2 h, and then treated with methyl iodide (3.6 ml, 57.4 mmol). The resulting mixture was heated under reflux for 10 h, and then treated with acetic acid (10 ml) and water (2 ml). Heating and stirring were continued overnight. The mixture was concentrated under vacuum and the residue partitioned between water (50 ml) and ethyl acetate (100 ml). The organic extract was collected and dried over magnesium sulphate. After concentration of the extract the residue was purified on silica gel using 80% isohexane/diethyl ether as eluent. The title compound was isolated as a colourless oil (1 g, 58%).

1. temperatureThe resulting mixture was heated
2. temperatureunder reflux for 10 h
3. temperatureHeating
4. stirringstirring
5. waitwere continued overnight
6. concentrationThe mixture was concentrated under vacuum
7. customthe residue partitioned between water (50 ml) and ethyl acetate (100 ml)
8. extractionThe organic extract
9. customwas collected
10. dry with materialdried over magnesium sulphate
11. extractionAfter concentration of the extract the residue
12. customwas purified on silica gel using 80% isohexane/diethyl ether as eluent

ORD record

ord-ce6dbff3665841e9be95dac261fe6775

Source dataset

uspto-grants-2005_10

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06953797B2