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

HRID 55893노트

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HRID 55893 반응식
[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]

참가 물질

4

반응물 2

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

생성물 1

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

시약·촉매·용매 1

HCID 6342Acetonitrile용매

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온도
100 °C

실험 절차

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+).

후처리

  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

출처 및 근거

ORD 기록
ord-da487a73894b48368f08579b2321b978
출처 데이터셋
uspto-grants-2016_09
특허 번호
US09433622B2

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