(3S)-pyrrolidin-3-ol → 6-Acetyl-3-((S)-3-hydroxy-pyrrolidin-1-yl)-pyridine-2-carbonitrile

HRID 55893ノート

反応式

HRID 55893 の反応式
[C:1]([C:4]1[N:9]=[C:8]([C:10]#[N:11])[C:7](Cl)=[CH:6][CH:5]=1)(=[O:3])[CH3:2].[NH:13]1[CH2:17][CH2:16][C@H:15]([OH:18])[CH2:14]1>CC#N>[C:1]([C:4]1[N:9]=[C:8]([C:10]#[N:11])[C:7]([N:13]2[CH2:17][CH2:16][C@H:15]([OH:18])[CH2:14]2)=[CH:6][CH:5]=1)(=[O:3])[CH3:2]

参加物

4

反応物 2

HCID 2733874(3S)-pyrrolidin-3-olHCID 903566946-Acetyl-3-chloropyridine-2-carbonitrile

生成物 1

HCID 903570016-Acetyl-3-((S)-3-hydroxy-pyrrolidin-1-yl)-pyridine-2-carbonitrile収率 64%

試薬・触媒・溶媒 1

HCID 6342Acetonitrile溶媒

反応条件

温度
100 °C

実験手順

6-Acetyl-3-chloro-pyridine-2-carbonitrile (64) (1.80 g, 9.97 mmol) was dissolved in MeCN (19 mL). (S)-3-Pyrrolidinol (884 μL, 10.9 mmol) and TEA (4.16 mL, 29.8 mmol) were added and the mixture stirred at 100° C. in the microwave for 20 minutes. The solvent was evaporated in vacuo and the crude material dissolved in EtOAc (100 mL). The solution was washed with 1:1 saturated brine solution-H2O (100 mL), saturated brine solution (100 mL), then dried (MgSO4), filtered and the solvent evaporated in vacuo. The crude product was purified by flash chromatography (Biotage SP1, 50 g SNAP cartridge) eluting with 6:4 isohexane-EtOAc→8:2 EtOAc-isohexane to yield the title compound as a yellow solid (1.32 g, 64%); LCMS, Rt=2.04 min (MeOH-FA method), m/z 232 (MH+).

後処理

  1. customThe solvent was evaporated in vacuo
  2. dissolutionthe crude material dissolved in EtOAc (100 mL)
  3. washThe solution was washed with 1:1 saturated brine solution-H2O (100 mL), saturated brine solution (100 mL)
  4. dry with materialdried (MgSO4)
  5. filtrationfiltered
  6. customthe solvent evaporated in vacuo
  7. customThe crude product was purified by flash chromatography (Biotage SP1, 50 g SNAP cartridge)
  8. washeluting with 6:4 isohexane-EtOAc→8:2 EtOAc-isohexane

出典と根拠

ORDレコード
ord-da487a73894b48368f08579b2321b978
出典データセット
uspto-grants-2016_09
特許番号
US09433622B2

反応ノート

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