Methanol → Cis-(6-benzhydryl-tetrahydropyran-3-yl)-[2-(4-fluorophenyl)-ethyl]-amine

Into a suspension of NaBH4 (0.21 g, 3.33 mmol) in dry THF (20 ml) was added BF3.Et2O drop wise at 0° C. The mixture was stirred for 1.5 Hours at room temperature and cooled to 0° C. A solution of cis-N-(6-benzhydryl-tetrahydropyran-3-yl)-2-(4-fluorophenyl)-acetamide 17 (0.17 g, 0.42 mmol) in dry THF (10 ml) was added dropwise into the solution. The mixture was refluxed overnight and cooled to room temperature. Methanol was added to quench the reaction followed by removal of solvent in vacuo. To the residue was added 20 ml 10% HCl/MeOH and the mixture refluxed for 1 hour. The reaction mixture was cooled down to room temperature and solid NaHCO3 was added at 0° C. to pH 9. The aqueous phase was extracted with dichloromethane (3×20 ml). The combined organic phases were dried over anhydrous Na2SO4, and the solvent was removed in vacuo. Flash chromatography gave 16p Cis-(6-benzhydryl-tetrahydropyran-3-yl)-[2-(4-fluorophenyl)-ethyl]-amine (0.13 g, yield 81%).

1. temperaturecooled to 0° C
2. temperatureThe mixture was refluxed overnight
3. temperaturecooled to room temperature
4. customto quench the reaction
5. customfollowed by removal of solvent in vacuo
6. additionTo the residue was added 20 ml 10% HCl/MeOH
7. temperaturethe mixture refluxed for 1 hour
8. temperatureThe reaction mixture was cooled down to room temperature
9. additionsolid NaHCO3 was added at 0° C. to pH 9
10. extractionThe aqueous phase was extracted with dichloromethane (3×20 ml)
11. dry with materialThe combined organic phases were dried over anhydrous Na2SO4
12. customthe solvent was removed in vacuo

ORD record

ord-1731daddedc04c29aa71092bf5504a35

Source dataset

uspto-grants-2014_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08841464B2