Oxalyl chloride → (4S)-4-benzyl-3-(5,5,5-trifluoropentanoyl)-1,3-oxazolidin-2-one

HRID 593472Notes

Reaction equation

HRID 593472 reaction equation
[F:1][C:2]([F:10])([F:9])[CH2:3][CH2:4][CH2:5][C:6]([OH:8])=O.C(Cl)(=O)C(Cl)=O.[CH2:17]([C@H:24]1[CH2:28][O:27][C:26](=[O:29])[NH:25]1)[C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1.[Li]CCCC>C(Cl)Cl.C1COCC1.CN(C=O)C>[CH2:17]([C@H:24]1[CH2:28][O:27][C:26](=[O:29])[N:25]1[C:6](=[O:8])[CH2:5][CH2:4][CH2:3][C:2]([F:1])([F:10])[F:9])[C:18]1[CH:19]=[CH:20][CH:21]=[CH:22][CH:23]=1

Participants

8

Reactant 4

HCID 65578Oxalyl chlorideHCID 736225(S)-4-Benzyl-2-oxazolidinoneHCID 27824465,5,5-trifluoropentanoic AcidHCID 178418339Butyllithium

Product 1

HCID 68314831(4S)-4-benzyl-3-(5,5,5-trifluoropentanoyl)-1,3-oxazolidin-2-one

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-78 °C

Procedure

To a stirring solution of 5,5,5-trifluoropentanoic acid (14.76 g, 95 mmol) and DMF (0.146 mL) in DCM (50 mL) was slowly added oxalyl chloride (8.27 mL, 95 mmol). After 2 h, the mixture was concentrated to dryness. A separate flask was changed with (S)-4-benzyloxazolidin-2-one (16.75 g, 95 mmol) in THF (100 mL) and then cooled to −78° C. To the solution was slowly added n-BuLi (2.5M, 37.8 mL, 95 mmol) over 10 min, stirred for 10 min, and then a solution of the above acid chloride in THF (50 mL) was slowly added over 5 min. The mixture was stirred for 30 min, and then warmed to room temperature. The mixture was quenched with saturated aqueous NH4Cl, 10% aqueous LiCl was then added, and the mixture was extracted with Et2O. The organic layer was washed with saturated aqueous NaHCO3 then with brine, dried (MgSO4), filtered and concentrated to dryness. The residue was purified by SiO2 chromatography (ISCO, 330 g column, eluting with a gradient from 100% hexane to 100% EtOAc) to afford the product Intermediate S-1B; (25.25 g, 85%): 1H NMR (400 MHz, CDCl3) δ ppm 7.32-7.39 (2 H, m), 7.30 (1 H, d, J=7.05 Hz), 7.18-7.25 (2 H, m), 4.64-4.74 (1 H, m), 4.17-4.27 (2 H, m), 3.31 (1 H, dd, J=13.35, 3.27 Hz), 3.00-3.11 (2 H, m), 2.79 (1 H, dd, J=13.35, 9.57 Hz), 2.16-2.28 (2 H, m), 1.93-2.04 (2 H, m).

Workup

  1. concentrationthe mixture was concentrated to dryness
  2. customover 10 min
  3. stirringThe mixture was stirred for 30 min
  4. temperaturewarmed to room temperature
  5. customThe mixture was quenched with saturated aqueous NH4Cl, 10% aqueous LiCl
  6. additionwas then added
  7. extractionthe mixture was extracted with Et2O
  8. washThe organic layer was washed with saturated aqueous NaHCO3
  9. dry with materialwith brine, dried (MgSO4)
  10. filtrationfiltered
  11. concentrationconcentrated to dryness
  12. customThe residue was purified by SiO2 chromatography (ISCO, 330 g column
  13. washeluting with a gradient from 100% hexane to 100% EtOAc)
  14. customto afford the product Intermediate S-1B

Sources & evidence

ORD record
ord-567475c96c584fbc878d2239c11f2fd5
Source dataset
uspto-grants-2016_01
Patent number
US09242940B2

Reaction notes

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