Acetic Acid → (R)-2-(((S)-3,3-Dimethyl-2,3-dihydro-1H-inden-1-yl)amino)-2-phenylethanol

HRID 222187

반응식

HRID 222187 반응식
[CH3:1][C:2]1([CH3:12])[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[C:4](=O)[CH2:3]1.[C:13]1([C@H:19]([CH2:21][OH:22])[NH2:20])[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1.C(O)(=O)C.[BH4-].[Na+]>C1(C)C=CC=CC=1.O.C1(C)C=CC(S(O)(=O)=O)=CC=1>[CH3:1][C:2]1([CH3:12])[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[C@@H:4]([NH:20][C@H:19]([C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)[CH2:21][OH:22])[CH2:3]1

참가 물질

7

반응물 4

HCID 176Acetic AcidHCID 3046283,3-Dimethyl-1-indanoneHCID 2724025(R)-beta-aminophenethyl alcoholHCID 4311764Sodium borohydride

생성물 1

HCID 66618252(R)-2-(((S)-3,3-Dimethyl-2,3-dihydro-1H-inden-1-yl)amino)-2-phenylethanol수율 91.8%

시약·촉매·용매 2

HCID 521998p-Toluenesulfonic acid monohydrate촉매HCID 1140Toluene용매2회

반응 조건

온도
0 °C

실험 절차

To a solution of 3,3-dimethylindan-1-one (925 mg, 5.77 mmol) and (R)-(−)-2-phenylglycinol (893 mg, 6.51 mmol) in toluene (10.0 mL) was added p-toluenesulfonic acid monohydrate (62.5 mg, 0.328 mmol). The reaction was heated to reflux under an atmosphere of nitrogen for 90 min. At this point, the mixture was cooled and diluted with toluene (10.0 mL). The mixture was washed with saturated aqueous sodium bicarbonate solution and water. The organic layer was concentrated in vacuo and the residue was dissolved in THF (10.0 mL) and cooled to 0° C. Acetic acid (1.13 mL, 19.9 mmol) was added, followed by sodium borohydride (251 mg, 6.64 mmol) and the reaction was allowed to warm to rt overnight. The mixture was partitioned between DCM and saturated aqueous sodium bicarbonate solution. The organic layer was concentrated and silica gel chromatography eluting with a gradient of 5 to 35% EtOAc in DCM afforded the title compound (1.49 g, 74%). LC/MS: Rt=1.92 min, ES+ 282 (AA standard).

후처리

  1. temperatureThe reaction was heated
  2. temperatureto reflux under an atmosphere of nitrogen for 90 min
  3. temperatureAt this point, the mixture was cooled
  4. washThe mixture was washed with saturated aqueous sodium bicarbonate solution and water
  5. concentrationThe organic layer was concentrated in vacuo
  6. dissolutionthe residue was dissolved in THF (10.0 mL)
  7. temperatureto warm to rt overnight
  8. customThe mixture was partitioned between DCM and saturated aqueous sodium bicarbonate solution
  9. concentrationThe organic layer was concentrated
  10. washsilica gel chromatography eluting with a gradient of 5 to 35% EtOAc in DCM

출처 및 근거

ORD 기록
ord-3d89567f7da2417cbe77edb6647d0cf3
출처 데이터셋
uspto-grants-2012_06
특허 번호
US08207177B2

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