Diethyl (cyanomethyl)phosphonate → HCID 69203761, compound

HRID 2378270Notes

Reaction equation

HRID 2378270 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]([F: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]([F: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 69205124HCID 69205124, compound

Product 1

HCID 69203761HCID 69203761, compoundYield 69%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a stirred solution of cyanomethylphosphonic acid diethyl ester (0.38 mL, 2.4 mmol) in THF (8 mL) in an ice bath was added lithium bis(trimethylsilyl)amide (1.0 M solution in THF, 2.3 mL, 2.3 mmol) dropwise. The mixture was stirred at room temperature for 40 min. (3-Ethoxy-4-methoxy-phenyl)-(3-fluoro-4-methoxy-phenyl)-methanone (0.35 mg, 1.2 mmol) was added to the mixture. The mixture was refluxed overnight. 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-(3-fluoro-4-methoxy-phenyl)-acrylonitrile as an off-white solid (0.26 g, 69% yield) (isomer ratio is 1:0.8 by HNMR): mp: 122-124° C.; 1H NMR (DMSO-d6) δ 1.31 (t, J=7 Hz, 3H, CH3), 3.78 (s, 3H, CH3), [4.83 and 3.87 (2s)], 3.94 (s, 3H, CH3), 4.01 (q, J=7 Hz, 2H, CH2), [6.15 (s)], 6.21 (s, 1H, CH), 6.74 (dd, J=2, 8 Hz, 1H, Ar), 6.92-7.36 (m, 5H, Ar); 13C NMR (DMSO-d6) δ 14.56, 14.58, 55.49, 56.08, 56.16, 63.84, 93.60, 93.82, 111.39, 111.59, 112.07, 113.53, 113.65, 113.75, 115.34, 115.64, 116.69, 116.99, 118.56, 122.27, 122.33, 125.70, 125.74, 120.22, 126.27, 128.84, 129.59, 129.70, 130.12, 130.86, 130.96, 147.47, 147.89, 148.12, 148.28, 148.88, 149.04, 149.18, 150.27, 151.18, 152.79, 153.06, 159.99, 160.09; Anal. Calcd for C19H18NO3F: C, 69.71; H, 5.54; N, 4.28. Found: C, 69.55; H, 5.58; N, 4.25.

Workup

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

Sources & evidence

ORD record
ord-cab1b0b2188e4ef1a1c945374c969fb4
Source dataset
uspto-grants-2008_12
Patent number
US07470723B2

Reaction notes

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