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

HRID 971018Notes

Reaction equation

HRID 971018 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])=[CH:15][CH:14]=2)=O)[CH:6]=[CH:7][C:8]=1[O:9][CH3:10].C(OP([CH2:29][C:30]#[N:31])(=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])=[CH:15][CH:14]=2)=[CH:29][C:30]#[N:31])[CH:6]=[CH:7][C:8]=1[O:9][CH3:10]

Participants

6

Reactant 4

HCID 75676Diethyl (cyanomethyl)phosphonateHCID 2733832Lithium HexamethyldisilazideHCID 2754574(3,4-Dimethoxyphenyl)(4-methoxyphenyl)methanoneHCID 692052993-(3,5-Dimethoxy-phenyl)-3-(3-methoxy-phenyl)-acrylonitrile

Product 1

HCID 692026013-(3,4-Dimethoxy-phenyl)-3-(4-methoxy-phenyl)-acrylonitrileYield 96%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

(3,4-dimethoxyphenyl)-(4-methoxyphenyl)methanone (2.00 g, 7.35 mmol), cyanomethylphosphonic acid diethyl ester (2.31 ml, 14.69 mmol) in anhydrous THF (10 ml), and lithium bis(trimethylsilyl)amide (1.0 M solution in THF, 14.69 ml, 14.69 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 30% EtOAc in hexane in about 40 min.) to give 3-(3,4-dimethoxy-phenyl)-3-(4-methoxy-phenyl)-acrylonitrile as a pink oil (2.08 g, 96%): 1HNMR (DMSO-d6) δ 7.34-6.7 (m, 7H, Ar), 6.14 (s, 0.50H, double bond proton of one isomer), 6.08 (s, 0.45H, double bond proton of the other isomer), 3.83-3.73 (multiple singlets, 9H, 3OCH3); 13C NMR(CDCl3)δ 162.6, 162.5, 161.6, 161.2, 151.2, 150.7, 149.0, 148.8, 132.2, 131.7, 131.5, 130.3, 129.8, 129.5, 123.2, 122.3, 118.8, 118.8, 114.1, 114.0, 112.9, 111.5, 110.9, 91.9, 91.8, 56.2, 56.1, 56.1, 55.5, 55.5; Anal. Calcd. For C18H17NO3: C, 71.92; H, 6.19; N, 4.32 (+0.04H2O). Found: C, 71.95; H, 6.04; N, 4.54.

Workup

  1. customThe crude was purified via flash column chromatography (5% EtOAc in hexane gradient to 30% EtOAc in hexane in about 40 min.)

Sources & evidence

ORD record
ord-acea74eee7024a84924725a3fd3dcf59
Source dataset
uspto-grants-2007_12
Patent number
US07312241B2

Reaction notes

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