Ethyl Acetate → HCID 44231035, compound

HRID 1907267Notes

Reaction equation

HRID 1907267 reaction equation
[Br:1][C:2]1[CH:7]=[CH:6][C:5]([C@@H:8]([N:10]([CH2:18][CH2:19][CH:20]([C:22]2[CH:27]=[CH:26][C:25]([F:28])=[CH:24][CH:23]=2)O)[C:11](=[O:17])[O:12]C(C)(C)C)[CH3:9])=[CH:4][CH:3]=1.[H-].[Na+].CCOC(C)=O>C1COCC1.O>[Br:1][C:2]1[CH:3]=[CH:4][C:5]([C@@H:8]([N:10]2[CH2:18][CH2:19][CH:20]([C:22]3[CH:23]=[CH:24][C:25]([F:28])=[CH:26][CH:27]=3)[O:12][C:11]2=[O:17])[CH3:9])=[CH:6][CH:7]=1

Participants

6

Reactant 3

HCID 8857Ethyl AcetateHCID 24758Sodium hydrideHCID 58200045HCID 58200045, compound

Product 1

HCID 44231035HCID 44231035, compound

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a stirred solution of tert-butyl (S)-1-(4-bromophenyl)ethyl(3-(4-fluorophenyl)-3-hydroxypropyl)carbamate (474 mg, 1.05 mmol) in dry THF (10 mL) was added 60% NaH in oil (250 mg, 10.4 mmol). The mixture was heated at reflux for 3 h. The mixture was diluted with water (20 mL) and. EtOAc (80 mL). The organic layer was separated, washed with 5% aq HCl (20 mL), satd aq NaHCO3 (20 mL) and brine (20 mL), and dried over Na2SO4. Removal of the solvent left an oil (348 mg). A portion of the crude product was purified by preparative HPLC to afford 3-((1S)-1-(4-bromophenyl)ethyl)-6-(4-fluorophenyl)-1,3-oxazinan-2-one as a 2:1 mixture of diastereomers based on 1H NMR. LC-MS (3 min) tR=1.92 min, m/z=380, 378. 1H NMR (CDCl3) S [selected resonances of major and minor diastereomers] 1.52 (d, major), 1.59 (d, minor), 3.06 (m, major), 3.31 (m, minor), 5.20 (dd, major), 5.25 (dd, minor).

Workup

  1. temperatureThe mixture was heated
  2. temperatureat reflux for 3 h
  3. customThe organic layer was separated
  4. washwashed with 5% aq HCl (20 mL)
  5. dry with materialdried over Na2SO4
  6. customRemoval of the solvent
  7. waitleft an oil (348 mg)
  8. customA portion of the crude product was purified by preparative HPLC

Sources & evidence

ORD record
ord-771686e9533e4ddeb62bb0146b37c076
Source dataset
uspto-grants-2013_12
Patent number
US08598160B2

Reaction notes

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