(S)-3-吡咯烷醇 → 6-Acetyl-3-((S)-3-hydroxy-pyrrolidin-1-yl)-pyridine-2-carbonitrile

HRID 55893笔记

反应方程式

HRID 55893 反应方程式
[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]

参与物

4

反应物 2

HCID 2733874(S)-3-吡咯烷醇HCID 903566946-Acetyl-3-chloropyridine-2-carbonitrile

产物 1

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

试剂、催化剂与溶剂 1

HCID 6342乙腈溶剂

反应条件

温度
100 °C

实验过程

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+).

后处理

  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

来源与证据

ORD记录
ord-da487a73894b48368f08579b2321b978
来源数据集
uspto-grants-2016_09
专利号
US09433622B2

反应笔记

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