Water → 2-chloro-3-(hydroxymethyl)-4-[(2S,3S)-3-(1-hydroxy-1-methylethyl)-2-methylpyrrolidin-1-yl]benzonitrile

HRID 2046689노트

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HRID 2046689 반응식
[Cl:1][C:2]1[C:9]([CH2:10][OH:11])=[C:8](F)[CH:7]=[CH:6][C:3]=1[C:4]#[N:5].[OH:13][C:14]([C@H:17]1[CH2:21][CH2:20][NH:19][C@H:18]1[CH3:22])([CH3:16])[CH3:15].C(=O)([O-])[O-].[Li+].[Li+].O>CS(C)=O>[Cl:1][C:2]1[C:9]([CH2:10][OH:11])=[C:8]([N:19]2[CH2:20][CH2:21][C@H:17]([C:14]([OH:13])([CH3:16])[CH3:15])[C@@H:18]2[CH3:22])[CH:7]=[CH:6][C:3]=1[C:4]#[N:5]

참가 물질

6

반응물 4

HCID 962WaterHCID 11125Lithium CarbonateHCID 55299039(2S,3S)-3-(1-hydroxy-1-methylethyl)-2-methylpyrrolidineHCID 593704972-Chloro-4-fluoro-3-(hydroxymethyl)benzonitrile

생성물 1

HCID 593705042-chloro-3-(hydroxymethyl)-4-[(2S,3S)-3-(1-hydroxy-1-methylethyl)-2-methylpyrrolidin-1-yl]benzonitrile수율 34.1%

시약·촉매·용매 1

HCID 679Dimethyl Sulfoxide용매

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온도
140 °C

실험 절차

To a solution (2 mL) of 2-chloro-4-fluoro-3-(hydroxymethyl)benzonitrile (150 mg) in dimethyl sulfoxide were added (2S,3S)-3-(1-hydroxy-1-methylethyl)-2-methylpyrrolidine 1/2 oxalate (167 mg) and lithium carbonate (66 mg), and the mixture was stirred at 140° C. for 10 min in a microwave reaction apparatus. Water was added and the mixture was extracted with ethyl acetate. The extract was washed with saturated brine, dried over anhydrous sodium sulfate and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (developing solvent: hexane:ethyl acetate=9:1→1:1) and recrystallized from ethyl acetate-isopropyl ether to give the compound as a pale-yellow solid (yield: 85 mg).

후처리

  1. extractionthe mixture was extracted with ethyl acetate
  2. washThe extract was washed with saturated brine
  3. dry with materialdried over anhydrous sodium sulfate
  4. concentrationconcentrated under reduced pressure
  5. customThe residue was purified by silica gel column chromatography (developing solvent: hexane:ethyl acetate=9:1→1:1)
  6. customrecrystallized from ethyl acetate-isopropyl ether

출처 및 근거

ORD 기록
ord-46a24537ca484f709cc7ddbc55f3c0b6
출처 데이터셋
uspto-grants-2013_11
특허 번호
US08592452B2

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