Hydrochloric Acid → HCID 15289505, compound

To a stirred solution of 3-[4-(4-chlorophenyl)-4-hydroxypiperidin-1-yl]propionitrile (3.51 g, 13.2 mmol, 1.0 equiv) in anhydrous THF (20 mL) under argon was added a solution of BH3 in THF (1.0M, 46.4 mL, 3.5 equiv) at room temperature. The mixture was refluxed for 4.5 hours and then cooled to room temperature. Aqueous HCl (6N, 30 mL) was added and stirring was continued for 2 hours at 55°-60° C. The mixture was basified to pH 9 by addition of 6N aq. NaOH and extracted with CH2Cl2 (3×150 mL). The combined organic solutions were dried over MgSO4 and concentrated. The residue was dissolved on CH2 Cl2 (20 mL) and treated with HCl in ether (1.0M, 27.7 mL, 2.1 equiv). The solvents were removed, ether (60 mL) was added, the mixture was filtered, and the filter cake was washed with ether (2×20 mL). Water (40 mL) was added to the resulting white solid, the pH was adjusted to 10 with 1M NaOH, and the aqueous phase was extracted with CH2Cl2 (3×80 mL). The combined organic solutions were dried over MgSO4 and concentrated to give 3.10 g (87%) of white solid, which was characterized spectroscopically.

1. temperatureThe mixture was refluxed for 4.5 hours
2. extractionextracted with CH2Cl2 (3×150 mL)
3. dry with materialThe combined organic solutions were dried over MgSO4
4. concentrationconcentrated
5. dissolutionThe residue was dissolved on CH2 Cl2 (20 mL)
6. customThe solvents were removed
7. additionether (60 mL) was added
8. filtrationthe mixture was filtered
9. washthe filter cake was washed with ether (2×20 mL)
10. additionWater (40 mL) was added to the resulting white solid
11. extractionthe aqueous phase was extracted with CH2Cl2 (3×80 mL)
12. dry with materialThe combined organic solutions were dried over MgSO4
13. concentrationconcentrated

ORD record

ord-f304b8963651428a9ebc96118cc57c9f

Source dataset

uspto-grants-1998_06

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US05767131