2-Chlorophenol → 1-Benzyl-4-(2-chlorophenoxy)piperidine

Triphenylphosphine (1.91 g, 7.31 mmol) was added to an ice-cooled solution of di-isopropylazodicarboxylate (1.48 g, 7.31 mmol) in dichloromethane (15 mL) and the mixture was stirred for 10 minutes. A solution of 2-chlorophenol (806 mg, 6.27 mmol) and 1-benzyl-4-hydroxypiperidine (1 g, 5.22 mmol) in dichloromethane (5 mL) was then added dropwise to the ice-cooled reaction mixture and stirring continued for a further 72 hours. The reaction mixture was then concentrated in vacuo and the residue was dissolved in diethyl ether and extracted with saturated citric acid solution (5×10 mL). The combined aqueous solution was then basified with sodium hydroxide and extracted with dichloromethane (2×20 mL). The combined organic solution was dried over magnesium sulfate and concentrated in vacuo to afford the title compound as a clear oil in 89% yield, 1.4 g. 1H NMR (CDCl3, 400 MHz) □: 1.85-1.95 (m, 2H), 1.97-2.08 (m, 2H), 2.32-2.47 (m, 2H), 3.58 (s, 2H), 4.46-4.34 (m, 1H), 6.87-6.95 (m, 2H), 7.16-7.22 (m, 1H), 7.20 (dd, 1H), 7.26-7.37 (m, 6H)

1. temperaturecooled
2. customreaction mixture
3. stirringstirring
4. waitcontinued for a further 72 hours
5. concentrationThe reaction mixture was then concentrated in vacuo
6. dissolutionthe residue was dissolved in diethyl ether
7. extractionextracted with saturated citric acid solution (5×10 mL)
8. extractionextracted with dichloromethane (2×20 mL)
9. dry with materialThe combined organic solution was dried over magnesium sulfate
10. concentrationconcentrated in vacuo

ORD record

ord-367f7f8c56594cf6a24cc3193d89a341

Source dataset

uspto-grants-2012_06

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08207198B2