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 (1.0 M, 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 (6 N, 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 6 N aq. NaOH and extracted with CH2Cl2 (3×150 mL). The combined organic solutions were dried over MgSO4 and concentrated. The residue was dissolved in CH2Cl2 (20 mL) and treated with HCl in ether (1.0 M, 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 1 M 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 in CH2Cl2 (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-f354f42bbdc642189a5864be415779a3

Source dataset

uspto-grants-2001_10

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06310076B1