Diethyl (cyanomethyl)phosphonate → 3-(2,5-Dimethoxy-phenyl)-3-(3,5-dimethoxy-phenyl)-acrylonitrile

HRID 970980Notes

Reaction equation

HRID 970980 reaction equation
[CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([O:9][CH3:10])=[CH:5][C:4]=1[C:11]([C:13]1[CH:18]=[C:17]([O:19][CH3:20])[CH:16]=[C:15]([O:21][CH3:22])[CH:14]=1)=O.C(OP([CH2:31][C:32]#[N:33])(=O)OCC)C.C[Si]([N-][Si](C)(C)C)(C)C.[Li+].O1C2C=CC(C(C3C=C(OC)C=C(OC)C=3)=CC#N)=CC=2OCC1>C1COCC1>[CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([O:9][CH3:10])=[CH:5][C:4]=1[C:11]([C:13]1[CH:18]=[C:17]([O:19][CH3:20])[CH:16]=[C:15]([O:21][CH3:22])[CH:14]=1)=[CH:31][C:32]#[N:33]

Participants

6

Reactant 4

HCID 75676Diethyl (cyanomethyl)phosphonateHCID 2733832Lithium HexamethyldisilazideHCID 692032153-(2,3-Dihydrobenzo[1,4]dioxin-6-yl)-3-(3,5-dimethoxyphenyl)acrylonitrileHCID 69203595(2,5-Dimethoxy-phenyl)-(3,5-dimethoxy-phenyl)-methanone

Product 1

HCID 692031833-(2,5-Dimethoxy-phenyl)-3-(3,5-dimethoxy-phenyl)-acrylonitrileYield 89%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

(2,5-dimethoxyphenyl)-(3,5-dimethoxyphenyl)methanone (0.92 g, 3.04 mmol), cyanomethylphosphonic acid diethyl ester (0.96 ml, 6.09 mmol) in anhydrous THF (15 ml), and lithium bis (trimethylsilyl)amide (1.0 M solution in THF, 6.09 ml, 6.09 mmol) were treated in the same manner as described above for the synthesis of 3-(2,3-dihydrobenzo[1,4]dioxin-6-yl)-3-(3,5-dimethoxyphenyl)acrylonitrile. The crude material was purified via flash column chromatography (10% EtOAc in hexane gradient to 25% EtOAc in hexane in about 20 min.) to give a brown oil, which was lyophilized to give 3-(2,5-dimethoxy-phenyl)-3-(3,5-dimethoxy-phenyl)-acrylonitrile as a light yellow solid (0.88 g, 89%): δ 1HNMR (CDCl3) δ 6.94-6.43 (m, 12H, Ar), 5.89 (s, 0.65H, double proton of one isomer), 5.87 (s, 0.84H, double proton of the other isomer), 3.83-3.67 (multiple singlets, 24H, 8OCH3). The product was a mixture of two isomers with the ratio of 43.6%:56.4%; 13C NMR (CDCl3) δ 161.0, 160.7, 159.9, 159.8, 153.6, 153.5, 151.9, 151.2, 140.3, 140.0, 128.9, 126.9, 117.9, 117.5, 117.3, 116.3, 116.2, 115.8, 113.2, 107.0, 105.8, 102.0, 102.0, 98.3, 97.4, 56.5, 56.0, 56.0, 55.6, 55.6; Anal. Calcd. For C19H19NO4: C, 70.14; H, 5.89; N, 4.30. Found: C, 69.78; H, 5.77; N, 4.20.

Workup

  1. customThe crude material was purified via flash column chromatography (10% EtOAc in hexane gradient to 25% EtOAc in hexane in about 20 min.)
  2. customto give a brown oil, which

Sources & evidence

ORD record
ord-537a1e52b5394706bacf0febcb6f53ad
Source dataset
uspto-grants-2007_12
Patent number
US07312241B2

Reaction notes

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