Diethyl (cyanomethyl)phosphonate → 3-(3,5-Dimethoxy-phenyl)-3-(3-ethoxy-4-methoxy-phenyl)-acrylonitrile

HRID 971020Notes

Reaction equation

HRID 971020 reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[C:5]([C:11]([C:13]2[CH:18]=[CH:17][C:16]([O:19][CH3:20])=[C:15]([O:21][CH2:22][CH3:23])[CH:14]=2)=O)[CH:6]=[C:7]([O:9][CH3:10])[CH:8]=1.C(OP([CH2:32][C:33]#[N:34])(=O)OCC)C.C[Si]([N-][Si](C)(C)C)(C)C.[Li+].COC1C=C(C(C2C=CC=C(OC)C=2)=CC#N)C=C(OC)C=1>C1COCC1>[CH3:1][O:2][C:3]1[CH:4]=[C:5]([C:11]([C:13]2[CH:18]=[CH:17][C:16]([O:19][CH3:20])=[C:15]([O:21][CH2:22][CH3:23])[CH:14]=2)=[CH:32][C:33]#[N:34])[CH:6]=[C:7]([O:9][CH3:10])[CH:8]=1

Participants

6

Reactant 4

HCID 75676Diethyl (cyanomethyl)phosphonateHCID 2733832Lithium HexamethyldisilazideHCID 69204482(3,5-Dimethoxyphenyl)-(3-ethoxy-4-methoxyphenyl)methanoneHCID 692052993-(3,5-Dimethoxy-phenyl)-3-(3-methoxy-phenyl)-acrylonitrile

Product 1

HCID 692050273-(3,5-Dimethoxy-phenyl)-3-(3-ethoxy-4-methoxy-phenyl)-acrylonitrileYield 89%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

(3,5-Dimethoxyphenyl)-(3-ethoxy-4-methoxyphenyl)methanone (0.63 g, 2.00 mmol), cyanomethylphosphonic acid diethyl ester (0.63 ml, 3.98 mmol) in anhydrous THF (10 ml), and lithium bis(trimethylsilyl)amide (1.0 M solution in THF, 3.98 ml, 3.98 mmol) were treated in the same manner as described above for the synthesis of 3-(3,5-dimethoxy-phenyl)-3-(3-methoxy-phenyl)-acrylonitrile. The crude was purified via flash column chromatography (5% EtOAc in hexane gradient to 40% EtOAc in hexane in about 40 min.) to give 3-(3,5-dimethoxy-phenyl)-3-(3-ethoxy-4-methoxy-phenyl)-acrylonitrile as an off-white solid (0.60 g, 89%): mp, 110-112° C.; 1HNMR (CDCl3) δ 7.04-6.82 (m, 3H, Ar), 6.55-6.43 (m, 3H, Ar), 5.65 (s, 0.50H, double bond proton of one isomer), 5.43 (s, 0.5H, double bond proton of the other isomer), 4.13-3.99 (m, 2H, CH2CH3 from the two isomers), 3.92 & 3.90 (s, 3H, single OCH3 group from the two isomers), 3.80 & 3.77 (s, 6H, 2OCH3 from the two isomers), 1.49-1.41 (two triplets, 3H, CH2CH3 from the two isomers); 13C NMR (CDCl3) δ 162.9, 162.8, 160.9, 160.8, 151.7, 151.1, 148.3, 148.0, 141.6, 139.1, 131.2, 129.3, 123.3, 122.2, 118.2, 114.2, 112.7, 111.2, 111.1, 107.8, 107.2, 102.3, 102.2, 93.8, 93.2, 64.7, 56.2, 56.1, 55.7, 14.8; Anal. Calcd. For C20H21NO4: C, 70.78; H, 6.24; N, 4.13. Found: C, 70.62; H, 6.25; N, 4.01.

Workup

  1. customThe crude was purified via flash column chromatography (5% EtOAc in hexane gradient to 40% EtOAc in hexane in about 40 min.)

Sources & evidence

ORD record
ord-a76a05a6439b46cbb70f57c1fcdd847c
Source dataset
uspto-grants-2007_12
Patent number
US07312241B2

Reaction notes

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