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

HRID 970984Notes

Reaction equation

HRID 970984 reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[C:5]([C:11]([C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][C:14]=2[O:19][CH3:20])=O)[CH:6]=[C:7]([O:9][CH3:10])[CH:8]=1.C(OP([CH2:29][C:30]#[N:31])(=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:4]=[C:5]([C:11]([C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][C:14]=2[O:19][CH3:20])=[CH:29][C:30]#[N:31])[CH:6]=[C:7]([O:9][CH3:10])[CH:8]=1

Participants

6

Reactant 4

HCID 75676Diethyl (cyanomethyl)phosphonateHCID 2733832Lithium HexamethyldisilazideHCID 692032153-(2,3-Dihydrobenzo[1,4]dioxin-6-yl)-3-(3,5-dimethoxyphenyl)acrylonitrileHCID 69203870(3,5-Dimethoxyphenyl)-(2-methoxyphenyl)methanone

Product 1

HCID 692033043-(3,5-Dimethoxy-phenyl)-3-(2-methoxy-phenyl)-acrylonitrileYield 70.3%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

(3,5-Dimethoxyphenyl)-(2-methoxyphenyl)methanone (1.22 g, 4.48 mmol), cyanomethylphosphonic acid diethyl ester (1.41 ml, 8.96 mmol) in anhydrous THF (30 ml), and lithium bis (trimethylsilyl)amide (1.0 M solution in THF, 9.00 ml, 9.00 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 30% EtOAc in hexane in about 30 min.) to give 3-(3,5-Dimethoxy-phenyl)-3-(2-methoxy-phenyl)-acrylonitrile as an off-white solid (0.93 g, 70%); mp, 82-84° C.: 1HNMR (CDCl3) 7.39-6.90 (m, 8H, Ar), 6.57 (d, J=2 Hz, 2H, Ar), 6.51-6.48 (m, 2H, Ar), 6.42 (d, J=2 Hz, 2H, Ar), 5.89 (s, 2H, double bond protons of the two isomers), 3.78 (s, 6H, 2OCH3), 3.75 (s, 6H, 2OCH3), 3.74 (s, 6H, 2OCH3); 13C NMR (CDCl3) δ 160.9, 160.7, 160.2, 159.9, 157.7, 140.6, 140.3, 131.6, 131.2, 130.9, 128.0, 126.2, 120.9, 120.7, 118.0, 117.6, 111.8, 107.1, 105.8, 101.9, 98.0, 97.3, 55.8, 55.6, 55.6; Anal. Calcd. For C18H17NO3: C, 73.20; H, 5.80; N, 4.74. Found: C, 73.08; H, 5.85; N, 4.78.

Workup

  1. customThe crude material was purified via flash column chromatography (10% EtOAc in hexane gradient to 30% EtOAc in hexane in about 30 min.)

Sources & evidence

ORD record
ord-cb1b4e212fb142b285a08aec7787eff3
Source dataset
uspto-grants-2007_12
Patent number
US07312241B2

Reaction notes

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