Diethyl Ether → (Z)-3-(3,5-dimethoxy-phenyl)-2-(5-methoxy-1H-indol-3-yl)-acrylonitrile

HRID 1503115Notes

Reaction equation

HRID 1503115 reaction equation
C[O-].[Na+].[CH3:4][O:5][C:6]1[CH:7]=[C:8]2[C:12](=[CH:13][CH:14]=1)[NH:11][CH:10]=[C:9]2[CH2:15][C:16]#[N:17].[CH3:18][O:19][C:20]1[CH:27]=[C:26]([O:28][CH3:29])[CH:25]=[CH:24][C:21]=1C=O.[CH2:30](OCC)C>C(O)C.C(Cl)Cl>[CH3:29][O:28][C:26]1[CH:25]=[C:24](/[CH:30]=[C:15](/[C:9]2[C:8]3[C:12](=[CH:13][CH:14]=[C:6]([O:5][CH3:4])[CH:7]=3)[NH:11][CH:10]=2)\[C:16]#[N:17])[CH:21]=[C:20]([O:19][CH3:18])[CH:27]=1

Participants

7

Reactant 4

HCID 3283Diethyl EtherHCID 691752,4-DimethoxybenzaldehydeHCID 35647832-(5-methoxy-1H-indol-3-yl)acetonitrileHCID 10942334Sodium Methoxide

Product 1

HCID 49854847(Z)-3-(3,5-dimethoxy-phenyl)-2-(5-methoxy-1H-indol-3-yl)-acrylonitrile

Reagents, catalysts & solvents 2

HCID 702EthanolSolvent2×HCID 6344DichloromethaneSolvent

Procedure

To a solution of sodium methanolate (61 mg, 1.1 mmol, 1.4 eq.) in anhydrous ethanol (10 mL) were added, under an argon atmosphere, (5-methoxy-1H-indol-3-yl)-acetonitrile (150 mg, 0.8 mmol, 1.0 eq.) and, after 30 minutes stirring, 2,4-dimethoxy-benzaldehyde (200 mg, 1.2 mmol, 1.5 eq.). The reaction apparatus was protected from light and the mixture stirred at room temperature for 3 days. The solvent was removed under reduced pressure and the residue purified by silica gel flash-column chromatography (eluent: CH2Cl2/EtOH, 100:0 to 98:2) to afford, after trituration with diethyl ether, the compound (14) as a yellow powder (85 mg, 32%). TLC: Rf=0.55 (CH2Cl2 96/EtOH, 4); mp: 141° C.; IR νmax (cm-1): 2212 (νCN), 3400 (νN—H); 1H NMR (DMSO, 300 MHz): δ (ppm): 3.81 (6H, s, 3″-methoxy and 5″-methoxy), 3.82 (3H, s, 5′-methoxy), 6.58 (1H, s, H4″), 6.89 (1H, dd, J6′-7′=8.9 Hz, J6′-4′=2.1 Hz, H6′), 7.11 and 7.12 (2H, m, H2″ and H6″), 7.39 (1H, d, J7′-6′=8.9 Hz, H7′), 7.44 (1H, d, J4′-6′=2.1 Hz, H4′), 7.64 (1H, s, H2′), 7.74 (1H, s, H3), 11.60 (1H, s, H indolic H); 13C NMR (DMSO, 75.5 MHz): δ (ppm): 55.8 (3″-methoxy and 5″-methoxy), 56.0 (5′-methoxy), 101.8 (C4′), 102.3 (C4″), 106.7 (C2), 107.0 (C2″ and C6″), 110.7 (C3′), 112.7 (C6′), 113.6 (C7′), 118.9 (C1), 124.5 (C3a′), 127.6 (C2′), 132.7 (C7a′), 136.5 (C3), 136.9 (C1″), 154.9 (C5′), 161.0 (C3″ and C5″); ESI-MS: m/z 357.1 ([M+Na]+); HRESI-MS: m/z 357.1219 (calcd for C20H18N2O3Na, 357.1205); Anal. Calcd for C20H18N2O2, 0.2H2O: C, 71.08; H, 5.49; N, 8.29; O, 15.15. Found: C, 70.89; H, 5.23; N, 8.34.

Workup

  1. customThe solvent was removed under reduced pressure
  2. customthe residue purified by silica gel flash-column chromatography (eluent: CH2Cl2/EtOH, 100:0 to 98:2)
  3. customto afford

Sources & evidence

ORD record
ord-27652b952de04e2aa5cf19b1593f7770
Source dataset
uspto-grants-2015_12
Patent number
US09212138B2

Reaction notes

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