Hydrochloric Acid → HCID 58651192, compound

Under a nitrogen atmosphere, to a solution of (2R)-2-Amino-1-[4-(2-methoxy-phenyl)-piperazin-1-yl]-3-pyridin-2-yl-propan-1-one (1.02 g; 3 mmol, from Example 12) in THF (10 mL) was added, dropwise, BF3.Et2O (0.37 mL; 3 mmol). The reaction mixture was heated to reflux, BH3.THF (1.0M/THF) (4.3 mL; 4.3 mmol) was added dropwise at reflux, and the mixture stirred at reflux for 2.5 hours. The mixture was cooled to 0–5° C., cautiously treated with 3N HCl (10 mL), stirred at ambient temperature for 1 hour. The mixture was heated to reflux for 5 minutes, cooled to ambient temperature, concentrated on a rotary evaporator to remove THF. The aqueous residue was washed with ether (5 mL), and the ether layer discarded. The aqueous layer was rendered basic (pH 9–10) with 2.5N NaOH, and the product extracted into ethyl acetate (25 mL). The organic layer was washed with brine, dried over MgSO4, filtered, and the solvent removed in vacuo to yield the free base of the title compound as an amber oil (804 mg; 82%), MS EI, M+ @ m/z 326; 1H NMR, 400 MHz, DMSO-d6.

1. temperatureThe reaction mixture was heated
2. temperatureto reflux
3. temperatureat reflux
4. temperatureat reflux for 2.5 hours
5. temperatureThe mixture was cooled to 0–5° C.
6. stirringstirred at ambient temperature for 1 hour
7. temperatureThe mixture was heated
8. temperatureto reflux for 5 minutes
9. concentrationconcentrated on a rotary evaporator
10. customto remove THF
11. washThe aqueous residue was washed with ether (5 mL)
12. extractionthe product extracted into ethyl acetate (25 mL)
13. washThe organic layer was washed with brine
14. dry with materialdried over MgSO4
15. filtrationfiltered
16. customthe solvent removed in vacuo

ORD record

ord-caf785670abc486db5d8cdf5311a2923

Source dataset

uspto-grants-2006_06

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07067518B2