Acetic Acid → HCID 86726358, compound

HRID 629754Notes

Reaction equation

HRID 629754 reaction equation
C[Si](C)(C)[N-][Si](C)(C)C.[Na+].[F:11][C:12]1[CH:13]=[C:14]([C@H:19]([C:35]2[CH:40]=[CH:39][C:38]([F:41])=[CH:37][CH:36]=2)[CH2:20][C:21]([N:23]2[C@@H:27]([C:28]3[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=3)[CH2:26][O:25][C:24]2=[O:34])=[O:22])[CH:15]=[C:16]([F:18])[CH:17]=1.CC(C1C=C(C(C)C)C(S([N:57]=[N+:58]=[N-:59])(=O)=O)=C(C(C)C)C=1)C.CC(O)=O>C1COCC1.C([O-])(=O)C.C[N+](C)(C)C>[N:57]([C@@H:20]([C@H:19]([C:14]1[CH:15]=[C:16]([F:18])[CH:17]=[C:12]([F:11])[CH:13]=1)[C:35]1[CH:36]=[CH:37][C:38]([F:41])=[CH:39][CH:40]=1)[C:21]([N:23]1[C@@H:27]([C:28]2[CH:29]=[CH:30][CH:31]=[CH:32][CH:33]=2)[CH2:26][O:25][C:24]1=[O:34])=[O:22])=[N+:58]=[N-:59]

Participants

7

Reactant 4

HCID 176Acetic AcidHCID 3717072,4,6-Triisopropylbenzenesulfonyl azideHCID 2724254Sodium bis(trimethylsilyl)amide2×HCID 90047910HCID 90047910, compound

Product 1

HCID 86726358HCID 86726358, compound

Reagents, catalysts & solvents 2

HCID 82741Tetramethylammonium acetateCatalystHCID 8028TetrahydrofuranSolvent3×

Procedure

10 mL of THF under an atmosphere of nitrogen was cooled to −78° C. in a dry ice-acetone bath and to the stirred solution was added sodium hexamethyldisilazide (9.1 mL of a 1.0 M solution in THF, 9.1 mmol). A solution of (4S)-3-[(3S)-3-(3,5-difluorophenyl)-3-(4-fluorophenyl)propanoyl]-4-phenyl-1,3-oxazolidin-2-one (3.5 g, 8.2 mmol) in 20 mL of THF under nitrogen atmosphere was cooled to −78° C. in a dry ice-acetone bath and added via cannula to the cold sodium hexamethyldisilazide solution. The resulting mixture was stirred at −78° C. for 30 min when trisyl azide (3.3 g, 11 mmol) was added as a solid. The solids dissolved and the cold solution was stirred for 2 min. To the cold solution was added HOAc (2.8 mL, 49 mmol) and solid tetramethylammonium acetate (4.4 g, 33 mmol). The cooling bath was removed and the mixture was stirred at ambient temperature for 4 h. The reaction was diluted with EtOAc and washed with brine. The aqueous phase was extracted with EtOAc, and the combined EtOAc layers were washed with aqueous Na HCO3 and brine, then dried (MgSO4), filtered, and the solvents were removed in vacuo. The residue was chromatographed on a 120 g SiO2 column using a gradient elution of 0-40% EtOAc in hexanes. Fractions containing product were combined and the solvents were removed in vacuo to give a solid.

Workup

  1. additionwas added as a solid
  2. dissolutionThe solids dissolved
  3. customThe cooling bath was removed
  4. stirringthe mixture was stirred at ambient temperature for 4 h
  5. additionThe reaction was diluted with EtOAc
  6. washwashed with brine
  7. extractionThe aqueous phase was extracted with EtOAc
  8. washthe combined EtOAc layers were washed with aqueous Na HCO3 and brine
  9. dry with materialdried (MgSO4)
  10. filtrationfiltered
  11. customthe solvents were removed in vacuo
  12. customThe residue was chromatographed on a 120 g SiO2 column
  13. washa gradient elution of 0-40% EtOAc in hexanes
  14. additionFractions containing product
  15. customthe solvents were removed in vacuo
  16. customto give a solid

Sources & evidence

ORD record
ord-f2a38012a9e74f7480b06fe38b0a9614
Source dataset
uspto-grants-2016_04
Patent number
US09315475B2

Reaction notes

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