Hydrochloric Acid → HCID 58109148, compound

To a solution of (R)-6-allyl-6-(4-fluorophenyl)-3-((S)-1-(3-fluorophenyl)ethyl)-1,3-oxazinan-2-one (80 mg, 0.392 mmol) in dry THF (4 mL) was added dropwise BH3.THF (0.2 mL, 0.2 mmol, 1 M) at 0° C. After stirring for 2 h at rt, the reaction mixture was cooled to 0° C. and water (1 mL), aqueous NaOH (0.5 mL, 3 M) and H2O2 (0.3 mL, 30%) were added successively. The mixture was stirred for 2-3 h at rt and diluted with water (8 mL). The pH was adjusted to 6-7 with 0.5 N aq HCl. The layers were separated, and the aqueous phase was extracted with EtOAc (3×6 mL). The combined organic layers were washed with a satd aq NaHCO3 (10 mL) and brine (10 mL), dried over Na2SO4, and concentrated in vacuo to give the crude product, which was purified by preparative TLC to afford (R)-6-(4-fluorophenyl)-3-((S)-1-(3-fluorophenyl)ethyl)-6-(3-hydroxypropyl)-1,3-oxazinan-2-one (40 mg, 48%). LC-MS Method 2 tR=2.151 min, m/z=332.1; 1H NMR (CDCl3): 1.31 (m, 1H) 1.49 (m, 3H), 1.64 (m, 1H), 1.81-1.93 (m, 2H), 2.14-2.26 (m, 3H), 2.88 (m, 1H), 3.51 (m, 2H), 5.68 (m, 1H), 6.96 (m, 2H), 7.13 (m, 1H), 7.19 (m, 4H), 7.37 (m, 1H).

1. temperaturethe reaction mixture was cooled to 0° C.
2. stirringThe mixture was stirred for 2-3 h at rt
3. customThe layers were separated
4. extractionthe aqueous phase was extracted with EtOAc (3×6 mL)
5. washThe combined organic layers were washed with a satd aq NaHCO3 (10 mL) and brine (10 mL)
6. dry with materialdried over Na2SO4
7. concentrationconcentrated in vacuo
8. customto give the crude product, which
9. customwas purified by preparative TLC

ORD record

ord-2dfccf44d12d4d3cbbcf15df2adccd26

Source dataset

uspto-grants-2013_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08575156B2