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

HRID 971009Notes

Reaction equation

HRID 971009 reaction equation
C(OP([CH2:9][C:10]#[N:11])(=O)OCC)C.C[Si]([N-][Si](C)(C)C)(C)C.[Li+].[CH3:22][O:23][C:24]1[CH:25]=[C:26]([C:32]([C:34]2[CH:39]=[CH:38][C:37]([O:40][CH3:41])=[CH:36][CH:35]=2)=O)[CH:27]=[C:28]([O:30][CH3:31])[CH:29]=1>C1COCC1>[CH3:22][O:23][C:24]1[CH:25]=[C:26]([C:32]([C:34]2[CH:35]=[CH:36][C:37]([O:40][CH3:41])=[CH:38][CH:39]=2)=[CH:9][C:10]#[N:11])[CH:27]=[C:28]([O:30][CH3:31])[CH:29]=1

Participants

5

Reactant 3

HCID 75676Diethyl (cyanomethyl)phosphonateHCID 2733832Lithium HexamethyldisilazideHCID 24261633(3,5-Dimethoxyphenyl)(4-methoxyphenyl)methanone

Product 1

HCID 692041093-(3,5-Dimethoxy-phenyl)-3-(4-methoxy-phenyl)-acrylonitrile

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a stirred solution of cyanomethylphosphonic acid diethyl ester (2.15 ml, 13.66 mmol) in anhydrous THF (10 ml) in an ice bath was added lithium bis(trimethylsilyl)amide (1.0 M solution in THF, 13.66 ml, 13.66 mmol) slowly. The mixture was stirred in rt for 40 min. To the mixture, a solution of (3,5-dimethoxyphenyl)-(4-methoxyphenyl)methanone (5193-23-B, 1.86 g, 6.83 mmol) in anhydrous THF (20 ml) was added. The mixture was refluxed overnight. The solution was poured into ice water (20 ml) and the two phases were separated. The THF phase was evaporated and combined with the aqueous phase, which were then extracted with CH2Cl2 (2×40 ml), washed with water (50 ml), dried over MgSO4, filtered and concentrated in vacuo to an oil, which was purified via flash column chromatography (20% EtOAc in hexane) to give 3-(3,5-Dimethoxy-phenyl)-3-(4-methoxy-phenyl)-acrylonitrile as a yellow oil which was solidified slowly (1.97 g, 98%): mp, 79-81° C.; 1HNMR (DMSO-d6) δ 7.35-7.31 (m, 2H, Ar), 7.07-6.96 (m, 2H, Ar), 6.65-6.62 (m, 1H, Ar), 6.46-6.44 (m, 2H, Ar), 6.23 (s, 0.43H, double bond H of one isomer), 6.20 (s, 0.58H, double bond H of the other isomer),3.82-3.68 (multiple singlets, 9H, OCH3); 13C NMR (CDCl3) 162.8, 162.6, 161.7, 161.3, 160.9, 160.8, 141.7, 139.2, 131.5, 131.0, 130.1, 129.3, 118.4, 118.2, 114.2, 114.0, 107.8, 107.2, 102.2, 102.1, 93.8, 93.0, 55.6, 55.5, 55.5; Anal. Calcd. for C18H17NO3+0.05H2O: C, 72.92; H, 5.89; N, 4.65. Found: C, 72.90; H, 5.52; N, 4.67.

Workup

  1. temperatureThe mixture was refluxed overnight
  2. customthe two phases were separated
  3. customThe THF phase was evaporated
  4. extractionwere then extracted with CH2Cl2 (2×40 ml)
  5. washwashed with water (50 ml)
  6. dry with materialdried over MgSO4
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo to an oil, which
  9. customwas purified via flash column chromatography (20% EtOAc in hexane)

Sources & evidence

ORD record
ord-ff5799b34c394d278446979c7f39d9ca
Source dataset
uspto-grants-2007_12
Patent number
US07312241B2

Reaction notes

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