Methyl Nicotinate → 3-hydroxy-2-(5-methoxy-1H-indol-3-yl)-3-(pyridin-3-yl)acrylonitrile

HRID 1503141Notes

Reaction equation

[H-].[Na+].[CH3:3][O:4][C:5]1[CH:6]=[C:7]2[C:11](=[CH:12][CH:13]=1)[NH:10][CH:9]=[C:8]2[CH2:14][C:15]#[N:16].[C:17](OC)(=[O:24])[C:18]1[CH:23]=[CH:22][CH:21]=[N:20][CH:19]=1.[Cl-].[NH4+]>C1COCC1>[OH:24][C:17]([C:18]1[CH:19]=[N:20][CH:21]=[CH:22][CH:23]=1)=[C:14]([C:8]1[C:7]2[C:11](=[CH:12][CH:13]=[C:5]([O:4][CH3:3])[CH:6]=2)[NH:10][CH:9]=1)[C:15]#[N:16]

Participants

Conditions

Temperature: 60 °C

Procedure

To a suspension of NaH (780 mg, 80%, 26 mmol, 1.6 eq.) in anhydrous THF (50 mL) were added, under an argon atmosphere, (5-methoxy-1H-indol-3-yl)-acetonitrile (3 g, 16 mmol, 1.0 eq.) and, after 30 minutes stirring at room temperature, methyl nicotinate (2.9 g, 21 mmol, 1.3 eq.). The reaction mixture was heated in a sealed tube at 60° C. for 13 hours. The reaction was allowed to cool to room temperature and then, treated with a saturated aqueous ammonium chloride solution. The mixture was extracted with ethyl acetate and the organic layer was washed with water and brine, and then dried over MgSO4. The solvent was removed under reduced pressure, and the residue purified by silica gel flash-column chromatography (eluent: CH2Cl2/EtOH, 96/4 to 95/5) to afford 3-hydroxy-2-(5-methoxy-1H-indol-3-yl)-3-(pyridin-3-yl)acrylonitrile as orange specks (2.5 g, 53%, E/Z ratio: 85/15).

Workup

additionwere added, under an argon atmosphere
temperatureto cool to room temperature
extractionThe mixture was extracted with ethyl acetate
washthe organic layer was washed with water and brine
dry with materialdried over MgSO4
customThe solvent was removed under reduced pressure
customthe residue purified by silica gel flash-column chromatography (eluent: CH2Cl2/EtOH, 96/4 to 95/5)

Sources & evidence

ORD record: ord-eb1156f8417b4d5180a7d490b6012719
Source dataset: uspto-grants-2015_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09212138B2

Reaction notes

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