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

HRID 2056365ノート

反応式

HRID 2056365 の反応式
[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

参加物

5

反応物 4

HCID 24813Phosphorus oxychlorideHCID 517045Sodium AcetateHCID 21187609acetonitrile N,N-dimethylacetamide2 回HCID 136358527HCID 136358527、化合物

生成物 1

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

実験手順

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)+.

後処理

  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

出典と根拠

ORDレコード
ord-d39048c7e72a4db281f171522e42e33e
出典データセット
uspto-grants-2008_02
特許番号
US07335666B2

反応ノート

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