Diethyl (cyanomethyl)phosphonate → 3-(3-Ethoxy-4-methoxy-phenyl)-3-(4-methoxy-3-methyl-phenyl)-acrylonitrile

HRID 2378278Notes

Reaction equation

HRID 2378278 reaction equation
C(OP([CH2:9][C:10]#[N:11])(=O)OCC)C.C[Si]([N-][Si](C)(C)C)(C)C.[Li+].[CH2:22]([O:24][C:25]1[CH:26]=[C:27]([C:33]([C:35]2[CH:40]=[CH:39][C:38]([O:41][CH3:42])=[C:37]([CH3:43])[CH:36]=2)=O)[CH:28]=[CH:29][C:30]=1[O:31][CH3:32])[CH3:23]>C1COCC1>[CH2:22]([O:24][C:25]1[CH:26]=[C:27]([C:33]([C:35]2[CH:40]=[CH:39][C:38]([O:41][CH3:42])=[C:37]([CH3:43])[CH:36]=2)=[CH:9][C:10]#[N:11])[CH:28]=[CH:29][C:30]=1[O:31][CH3:32])[CH3:23]

Participants

5

Reactant 3

HCID 75676Diethyl (cyanomethyl)phosphonateHCID 2733832Lithium HexamethyldisilazideHCID 69205620HCID 69205620, compound

Product 1

HCID 692040293-(3-Ethoxy-4-methoxy-phenyl)-3-(4-methoxy-3-methyl-phenyl)-acrylonitrileYield 75%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a stirred solution of cyanomethylphosphonic acid diethyl ester (1.3 mL, 8.3 mmol) in THF (20 mL) in an ice bath was added lithium bis(trimethylsilyl)amide (1.0 M solution in THF, 8.3 mL, 8.3 mmol) dropwise. The mixture was stirred at room temperature for 40 min. A solution of (3-ethoxy-4-methoxy-phenyl)-(4-methoxy-3-methyl-phenyl)-methanone from above in THF (10 mL) was added to the mixture. The mixture was refluxed for 4 h. The solution was poured into ice water (30 mL). The aqueous layer was extracted with ethyl acetate (2×50 mL). The combined organic layers was washed with water (50 mL), sodium hydrogen carbonate (50 mL, sat), brine (50 mL) and dried over magnesium sulfate. Removal of solvent and chromatography (Silica Gel) gave a mixture of (E/Z) 3-(3-ethoxy-4-methoxy-phenyl)-3-(4-methoxy-3-methyl-phenyl)-acrylonitrile as a white solid (0.97 g, 75% yield) (isomer ratio is 1:0.8 by HNMR): mp: 86-88° C.; 1H NMR (DMSO-d6) δ 1.30 (t, J=7 Hz, 3H, CH3), 2.13 (s, 3H, CH3), [2.17 (s)], 3.78 (s, 3H, CH3), 3.82 (s, 3H, CH3), [3.83 (s), 3.86 (s)], 3.93-4.04 (m, 2H, CH2), 6.01 (s, 1H, CH), [6.08 (s)], 6.72-7.26 (m, 6H, Ar); 13C NMR (DMSO-d6) 14.56, 14.59, 15.98, 63.77, 92.10, 92.42, 110.04, 110.18, 111.35, 111.51, 112.27, 113.83, 118.92, 122.27, 122.35, 125.61, 125.86, 128.05, 128.60, 128.92, 129.44, 130.14, 130.35, 130.82, 131.29, 147.36, 147.78, 150.15, 151.02, 158.44, 159.28, 161.47, 161.53; Anal. Calcd for C20H21NO3: C, 74.28; H, 6.55; N, 4.33. Found: C, 74.16; H, 6.48; N, 4.30.

Workup

  1. temperatureThe mixture was refluxed for 4 h
  2. extractionThe aqueous layer was extracted with ethyl acetate (2×50 mL)
  3. washThe combined organic layers was washed with water (50 mL), sodium hydrogen carbonate (50 mL, sat), brine (50 mL)
  4. dry with materialdried over magnesium sulfate
  5. customRemoval of solvent and chromatography (Silica Gel)
  6. customgave

Sources & evidence

ORD record
ord-805c45153848400eb3afa00510a4d139
Source dataset
uspto-grants-2008_12
Patent number
US07470723B2

Reaction notes

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