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

HRID 55893

Reaction equation

[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]

Participants

Conditions

Temperature: 100 °C

Procedure

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+).

Workup

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

Sources & evidence

ORD record: ord-da487a73894b48368f08579b2321b978
Source dataset: uspto-grants-2016_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09433622B2

Linked notes

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