Phosphorus oxychloride → [2-Methyl-7,8-dihydro[1,4]dioxino[2,3-g][1,3]benzoxazol-8-yl]methanol

HRID 2056365노트

반응식

HRID 2056365 반응식
[OH:1][C:2]1[C:11]2[O:10][C@@H:9]([CH2:12][OH:13])[CH2:8][O:7][C:6]=2[CH:5]=[CH:4][C:3]=1C(=NO)C.P(Cl)(Cl)(Cl)=O.C([O-])(=O)C.[Na+].C[N:29](C)[C:30](=O)[CH3:31].C(#N)C>>[CH3:31][C:30]1[O:1][C:2]2[C:11]3[O:10][CH:9]([CH2:12][OH:13])[CH2:8][O:7][C:6]=3[CH:5]=[CH:4][C:3]=2[N:29]=1

참가 물질

5

반응물 4

HCID 24813Phosphorus oxychlorideHCID 517045Sodium AcetateHCID 21187609acetonitrile N,N-dimethylacetamide2회HCID 1363585271-[(3S)-5-hydroxy-3-(hydroxymethyl)-2,3-dihydro-1,4-benzodioxin-6-yl]-1-ethanone oxime

생성물 1

HCID 21892056[2-Methyl-7,8-dihydro[1,4]dioxino[2,3-g][1,3]benzoxazol-8-yl]methanol

실험 절차

3.03 g (12.6 mmole) of 1-[(3S)-5-hydroxy-3-(hydroxymethyl)-2,3-dihydro-1,4-benzodioxin-6-yl]-1-ethanone oxime was dissolved in a mixture of 1:3 N,N-dimethylacetamide/acetonitrile (100 mL). The solution was cooled in an ice/water bath and a solution of phosphorus oxychloride-(1.26 mL, 35 mmole) in 1:3 N,N-dimethylacetamide/acetonitrile (30 mL) was added. The reaction mixture was stirred under nitrogen over a period of 48 hours. It was then added to an ice cold, saturated solution of sodium acetate, extracted with ethyl acetate, dried over magnesium sulfate, filtered and evaporated in vacuum. The resulting crude oil was column chromatographed on silica gel with 60% hexane/ethyl acetate to remove impurities and the product eluted with 40% hexane/ethyl acetate. After evaporation of the solvent in vacuum, 2.08 g (75%) of the (S)-enantiomer of the title compound was obtained as a white solid, m.p. 120° C. MS (ESI) m/z 222 (M+H)+.

후처리

  1. temperatureThe solution was cooled in an ice/water bath
  2. extractionextracted with ethyl acetate
  3. dry with materialdried over magnesium sulfate
  4. filtrationfiltered
  5. customevaporated in vacuum
  6. customchromatographed on silica gel with 60% hexane/ethyl acetate
  7. customto remove impurities
  8. washthe product eluted with 40% hexane/ethyl acetate
  9. customAfter evaporation of the solvent in vacuum, 2.08 g (75%) of the (S)-enantiomer of the title compound
  10. customwas obtained as a white solid, m.p. 120° C

출처 및 근거

ORD 기록
ord-d39048c7e72a4db281f171522e42e33e
출처 데이터셋
uspto-grants-2008_02
특허 번호
US07335666B2

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