Borane;tetrahydrofuran → (R)-3-((S)-1-(4-bromophenyl)ethyl)-6-(4-fluorophenyl)-6-(3-hydroxy-propyl)-1,3-oxazinan-2-one

To a solution of (R)-6-allyl-3-((S)-1-(4-bromophenyl)ethyl)-6-(4-fluorophenyl)-1,3-oxazinan-2-one (2.0 g, 4.8 mmol) in THF (48 ml) was added BH3.THF (5.7 ml, 1 mol/L) at 0° C. under nitrogen atmosphere, and the resulting solution was stirred for 2 h at rt. The reaction was quenched with water. Then aqueous NaOH solution (2.0 ml, 3 mol/L) and H2O2 (2 mL, 30%) were added to the mixture. The resulting mixture was stirred for 2 h at rt. The mixture was diluted with EtOAc, and the pH was adjusted to 6-7 with 1M aq HCl. The aqueous phase was extracted with EtOAc, and the combined organic phase was washed with satd aq NaHCO3 and brine, dried over Na2SO4, concentrated to give the crude product, which was purified on silica gel to give (R)-3-((S)-1-(4-bromophenyl)ethyl)-6-(4-fluorophenyl)-6-(3-hydroxypropyl)-1,3-oxazinan-2-one (1.13 g, 54%). 1H NMR: (400 MHz, CDCl3): 1.32 (m, 1H), 1.43 (d, 3H), 1.63 (m, 1H), 1.90 (m, 2H), 2.21 (m, 3H), 2.84 (m, 1H), 3.51 (t, 2H), 5.54 (q, 1H), 6.72 (d, 2H), 6.98 (t, 2H), 7.18 (m, 4H).

1. customThe reaction was quenched with water
2. additionThen aqueous NaOH solution (2.0 ml, 3 mol/L) and H2O2 (2 mL, 30%) were added to the mixture
3. stirringThe resulting mixture was stirred for 2 h at rt
4. additionThe mixture was diluted with EtOAc
5. extractionThe aqueous phase was extracted with EtOAc
6. washthe combined organic phase was washed with satd aq NaHCO3 and brine
7. dry with materialdried over Na2SO4
8. concentrationconcentrated
9. customto give the crude product, which
10. customwas purified on silica gel

ORD record

ord-86fb326f8ad0413d9fec6ea5f546736c

Source dataset

uspto-grants-2013_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08575156B2