Carbon Dioxide → (S)-3-(3-Fluoro-4-methyl-phenyl)-5-hydroxymethyl-oxazolidin-2-one

HRID 527956

반응식

HRID 527956 반응식
[F:1][C:2]1[CH:3]=[C:4]([CH:6]=[CH:7][C:8]=1[CH3:9])[NH2:5].[C:10]([O-:13])(O)=[O:11].[Na+].ClC([O:18][CH2:19][C:20]1C=CC=C[CH:21]=1)=O.C(=O)=O.[Li]CCCC.C(OC[C@H]1OC1)(=O)CCC.C([O-])([O-])=O.[Cs+].[Cs+].[NH4+].[Cl-]>CC(=O)OCC.CC(C)=O>[F:1][C:2]1[CH:3]=[C:4]([N:5]2[CH2:21][C@@H:20]([CH2:19][OH:18])[O:13][C:10]2=[O:11])[CH:6]=[CH:7][C:8]=1[CH3:9]

참가 물질

11

반응물 8

HCID 280Carbon DioxideHCID 99573-Fluoro-4-methylanilineHCID 10387Benzyl chloroformateHCID 10796Cesium carbonateHCID 25517Ammonium ChlorideHCID 516892Sodium BicarbonateHCID 6999819(S)-(+)-Glycidyl butyrateHCID 178418339Butyllithium

생성물 1

HCID 66953644(S)-3-(3-Fluoro-4-methyl-phenyl)-5-hydroxymethyl-oxazolidin-2-one수율 53%

시약·촉매·용매 2

HCID 180Acetone용매HCID 8857Ethyl Acetate용매

실험 절차

A mixture of 3-fluoro-4-methyl-aniline (commercial; 1.25 g, 10 mmol), sat. aq. NaHCO3 (10 mL) and acetone (10 mL) was treated dropwise with benzyl chloroformate (1.70 g, 1.41 mL, 1 eq.). After CO2 evolution ceased, the mixture was partitioned between EA and sat. aq. NaHCO3, the org. layer was dried over MgSO4 and concentrated under reduced pressure. The resulting benzyl carbamate was dissolved in THF (50 mL) and cooled under argon to −78° C. n-BuLi (2.5M in Hex, 6.45 mL, 1.1 eq.) was added dropwise, and the resulting solution was stirred for 1 h at that temperature. The reaction was then allowed to warm to −15° C. at which (S)-glycidyl butyrate (1.69 mL, 1.1 eq.) was added dropwise. The mixture was stirred at rt overnight. A tip of a spatula of Cs2CO3 was added, and the mixture was stirred at rt for 3 h. NH4Cl and EA were added and the phases were separated. The aq. phase was extracted once more with EA and the combined org. extracts were washed several times with sat. aq. NH4Cl, then with brine, dried over Na2SO4 and concentrated. The orange solid obtained was triturated with EA to afford the title intermediate as a pale yellow solid (1.18 g, 53% yield).

후처리

  1. customthe mixture was partitioned between EA and sat. aq. NaHCO3
  2. dry with materiallayer was dried over MgSO4
  3. concentrationconcentrated under reduced pressure
  4. dissolutionThe resulting benzyl carbamate was dissolved in THF (50 mL)
  5. additionwas added dropwise
  6. additionwas added dropwise
  7. stirringThe mixture was stirred at rt overnight
  8. stirringthe mixture was stirred at rt for 3 h
  9. customthe phases were separated
  10. extractionThe aq. phase was extracted once more with EA
  11. washextracts were washed several times with sat. aq. NH4Cl
  12. dry with materialwith brine, dried over Na2SO4
  13. concentrationconcentrated
  14. customThe orange solid obtained
  15. customwas triturated with EA

출처 및 근거

ORD 기록
ord-72674db44b79401eb3bcb20922bc8342
출처 데이터셋
uspto-grants-2016_05
특허 번호
US09346804B2

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