Hydrochloric Acid → (S)-3,3-dimethylbutan-2-yl-6-(4-fluorophenyl)-6-(3-hydroxypropyl)-1,3-oxazinan-2-one

HRID 403582Notes

Reaction equation

HRID 403582 reaction equation
[CH2:1]([C@@:4]1([C:17]2[CH:22]=[CH:21][C:20]([F:23])=[CH:19][CH:18]=2)[O:9][C:8](=[O:10])[N:7]([C@H:11]([C:13]([CH3:16])([CH3:15])[CH3:14])[CH3:12])[CH2:6][CH2:5]1)[CH:2]=[CH2:3].B.C1C[O:28]CC1.[OH-].[Na+].OO.Cl>C1COCC1.O>[CH3:14][C:13]([CH3:15])([CH3:16])[CH:11]([N:7]1[CH2:6][CH2:5][C@:4]([C:17]2[CH:18]=[CH:19][C:20]([F:23])=[CH:21][CH:22]=2)([CH2:1][CH2:2][CH2:3][OH:28])[O:9][C:8]1=[O:10])[CH3:12]

Participants

8

Reactant 5

HCID 313Hydrochloric AcidHCID 784Hydrogen PeroxideHCID 14798Sodium HydroxideHCID 2723981Borane;tetrahydrofuranHCID 58485275(R)-6-allyl-3-((S)-3,3-dimethylbutan-2-yl)-6-(4-fluorophenyl)-1,3-oxazinan-2-one

Product 1

HCID 86696536(S)-3,3-dimethylbutan-2-yl-6-(4-fluorophenyl)-6-(3-hydroxypropyl)-1,3-oxazinan-2-oneYield 2.1%

Reagents, catalysts & solvents 2

HCID 962WaterSolvent2×HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of (R)-6-allyl-3-((S)-3,3-dimethylbutan-2-yl)-6-(4-fluorophenyl)-1,3-oxazinan-2-one (90 mg, 0.28 mmol) in dry THF (5 mL) was added dropwise 1 M BH3.THF (0.56 mL, 0.564 mmol) at 0° C. After stirring for 2 h at rt, the reaction mixture was cooled to 0° C. and water (1 mL), 3 M aqueous NaOH (0.5 mL) and 30% H2O2 (0.5 mL) were successively added. The mixture was stirred for 2-3 h at rt and was then diluted with water (6 mL). The pH was adjusted to 6-7 with 0.5 N HCl. The aqueous phase was extracted with EtOAc (3×5 mL). The combined organic layers were washed with saturated aqueous NaHCO3 solution (8 mL) and brine (8 mL), dried over Na2SO4, and concentrated in vacuo to give the crude product, which was purified by preparative TLC to afford (R)-3-((S)-3,3-dimethylbutan-2-yl-6-(4-fluorophenyl)-6-(3-hydroxypropyl)-1,3-oxazinan-2-one (2 mg, 2%). LC-MS Method 1 tR=1.179, min, m/z=338.1; 1H NMR (CDCl3) 0.65 (s, 9H), 0.99-1.06 (d, 3H), 1.18 (m, 1H), 1.29 (m, 1H), 1.61-1.71 (m, 1H), 1.83-2.08 (m, 3H), 2.21-2.28 (m, 1H), 2.62-2.73 (m, 1H), 3.06-3.13 (m, 1H), 3.47-3.53 (m, 2H), 4.36-4.43 (m, 1H), 6.98-7.06 (m, 2H), 7.22-7.26 (m, 2H)

Workup

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

Sources & evidence

ORD record
ord-3d848cc284234c6fa903d3a862331064
Source dataset
uspto-grants-2014_06
Patent number
US08748444B2

Reaction notes

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