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

HRID 2046689ノート

反応式

HRID 2046689 の反応式
[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]

参加物

6

反応物 4

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

生成物 1

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

試薬・触媒・溶媒 1

HCID 679Dimethyl Sulfoxide溶媒

反応条件

温度
140 °C

実験手順

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).

後処理

  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

出典と根拠

ORDレコード
ord-46a24537ca484f709cc7ddbc55f3c0b6
出典データセット
uspto-grants-2013_11
特許番号
US08592452B2

反応ノート

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