Phenylacetyl chloride → (4R)-4-Benzyl-3-(phenylacetyl)-1,3-oxazolidin-2-one

HRID 2276859Notes

Reaction equation

HRID 2276859 reaction equation
[CH2:1]([C@@H:8]1[CH2:12][O:11][C:10](=[O:13])[NH:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[Li]CCCC.[C:19]1([CH2:25][C:26](Cl)=[O:27])[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1>C1COCC1>[CH2:1]([C@@H:8]1[CH2:12][O:11][C:10](=[O:13])[N:9]1[C:26](=[O:27])[CH2:25][C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

5

Reactant 3

HCID 7679Phenylacetyl chlorideHCID 2734969(R)-4-Benzyl-2-oxazolidinoneHCID 178418339Butyllithium

Product 1

HCID 15597772(4R)-4-Benzyl-3-(phenylacetyl)-1,3-oxazolidin-2-one

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a cold (−78° C.), stirred solution of (4R)-4-benzyl-1,3-oxazolidin-2-one (4.17 g, 23.53 mmol) in THF (100 mL) under nitrogen atmosphere was added n-BuLi (9.5 mL, 23.75 mmol) dropwise via syringe over 10 min. After stirring for 10 min, a solution of 2-phenylacetyl chloride (3.2 mL, 24.20 mmol) in THF (20 mL) was added via cannula over 10 min. After the addition was complete, the reaction mixture was placed in an ice-water bath and was stirred at 0° C. for 1 hr, then removed from the ice bath. To the reaction mixture was added aqueous saturated NH4Cl and was extracted with EtOAc (2×). The combined organics were washed with brine, dried (Na2SO4), filtered and concentrated under reduced pressure. The residue was purified by flash chromatography (Teledyne ISCO CombiFlash Rf, 0% to 100% solvent hexanes/EtOAc, REDISEP® SiO2 120 g). Concentration of appropriate fractions provided Preparation 4E (6.19 g, 89%) as a colorless viscous oil: 1H NMR (400 MHz, CDCl3) δ 7.32-7.39 (4H, m), 7.21-7.32 (4H, m), 7.10-7.17 (2H, m), 4.67 (1H, dddd, J=10.29, 6.34, 3.45, 3.26 Hz), 4.30 (2H, q, J=15.56 Hz), 4.15-4.22 (2H, m), 3.26 (1H, dd, J=13.30, 3.26 Hz), 2.76 (1H, dd).

Workup

  1. additionAfter the addition
  2. customthe reaction mixture was placed in an ice-water bath
  3. stirringwas stirred at 0° C. for 1 hr
  4. customremoved from the ice bath
  5. additionTo the reaction mixture was added aqueous saturated NH4Cl
  6. extractionwas extracted with EtOAc (2×)
  7. washThe combined organics were washed with brine
  8. dry with materialdried (Na2SO4)
  9. filtrationfiltered
  10. concentrationconcentrated under reduced pressure
  11. customThe residue was purified by flash chromatography (Teledyne ISCO CombiFlash Rf, 0% to 100% solvent hexanes/EtOAc, REDISEP® SiO2 120 g)
  12. customConcentration of appropriate fractions provided

Sources & evidence

ORD record
ord-f37be3ca7caa48248e185d985791d253
Source dataset
uspto-grants-2015_09
Patent number
US09133139B2

Reaction notes

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