Diethyl (cyanomethyl)phosphonate → 3-[3-(5-Ethyl-2,6-dimethoxy-pyrimidine-4-carbonyl)-5-methyl-phenyl]-acrylonitrile

HRID 426187Notes

Reaction equation

HRID 426187 reaction equation
[CH2:1]([C:3]1[C:4]([C:13]([C:15]2[CH:16]=[C:17]([CH:20]=[C:21]([CH3:23])[CH:22]=2)[CH:18]=O)=[O:14])=[N:5][C:6]([O:11][CH3:12])=[N:7][C:8]=1[O:9][CH3:10])[CH3:2].[C:24]([CH2:26]P(=O)(OCC)OCC)#[N:25].CC(C)([O-])C.[K+]>C1COCC1>[CH2:1]([C:3]1[C:4]([C:13]([C:15]2[CH:16]=[C:17]([CH:18]=[CH:26][C:24]#[N:25])[CH:20]=[C:21]([CH3:23])[CH:22]=2)=[O:14])=[N:5][C:6]([O:11][CH3:12])=[N:7][C:8]=1[O:9][CH3:10])[CH3:2]

Participants

5

Reactant 3

HCID 75676Diethyl (cyanomethyl)phosphonateHCID 23665647Potassium tert-butoxideHCID 591848303-(5-Ethyl-2,6-dimethoxy-pyrimidine-4-carbonyl)-5-methyl-benzaldehyde

Product 1

HCID 667055223-[3-(5-Ethyl-2,6-dimethoxy-pyrimidine-4-carbonyl)-5-methyl-phenyl]-acrylonitrileYield 72%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a stirred mixture of 3-(5-ethyl-2,6-dimethoxy-pyrimidine-4-carbonyl)-5-methyl-benzaldehyde (3.11 g, 9.9 mmol) and diethyl cyanomethyl-phosphonate (1.6 ml, 10 mmol) in anhydrous THF (20 ml) at 0° C. (ice bath) under nitrogen atmosphere, was added potassium t-butoxide (1.26 g, 11.2 mmol). After 1 hr., the mixture was stirred at room temperature for 5 hr. The mixture was then partitioned between ether and water. The ether layer was taken, dried with anhydrous magnesium sulfate, filtered, and evaporated in vacuo to give a pale yellow syrup. The crude product was purified by silica gel column chromatography (eluent, EA:hexanes (1:4)) to afford 2.39 g (72%) of a white solid. m.p. 165-166° C.; 1H NMR (200 MHz, CDCl3) δ 1.09 (3H, t, J=7.8 Hz), 2.42-2.53 (5H, m), 3.96 (3H, s), 4.09 (3H, s), 5.93 (1H, d, J=16.8 Hz), 7.40 (1H, s, J=16.8 Hz), 7.50 (1H, s), 7.73 (1H, s), 7.79 (1H, s).

Workup

  1. customThe mixture was then partitioned between ether and water
  2. dry with materialdried with anhydrous magnesium sulfate
  3. filtrationfiltered
  4. customevaporated in vacuo
  5. customto give a pale yellow syrup
  6. customThe crude product was purified by silica gel column chromatography (eluent, EA:hexanes (1:4))

Sources & evidence

ORD record
ord-9371bccb9ea64dc383f4d0fbce7f8271
Source dataset
uspto-grants-2012_01
Patent number
US08106064B2

Reaction notes

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