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

HRID 426177Notes

Reaction equation

HRID 426177 reaction equation
[CH:1]([C:4]1[C:5]([C:14]([C:16]2[CH:17]=[C:18]([CH:21]=[C:22]([CH3:24])[CH:23]=2)[CH:19]=O)=[O:15])=[N:6][C:7]([O:12][CH3:13])=[N:8][C:9]=1[O:10][CH3:11])([CH3:3])[CH3:2].[C:25]([CH2:27]P(=O)(OCC)OCC)#[N:26].CC(C)([O-])C.[K+]>C1COCC1.CCOCC>[CH:1]([C:4]1[C:5]([C:14]([C:16]2[CH:17]=[C:18]([CH:19]=[CH:27][C:25]#[N:26])[CH:21]=[C:22]([CH3:24])[CH:23]=2)=[O:15])=[N:6][C:7]([O:12][CH3:13])=[N:8][C:9]=1[O:10][CH3:11])([CH3:2])[CH3:3]

Participants

6

Reactant 3

HCID 75676Diethyl (cyanomethyl)phosphonateHCID 23665647Potassium tert-butoxideHCID 591848613-(5-Isopropyl-2,6-dimethoxy-pyrimidine-4-carbonyl)-5-methyl-benzaldehyde

Product 1

HCID 667055443-[3-(5-Isopropyl-2,6-dimethoxy-pyrimidine-4-carbonyl)-5-methyl-phenyl]-acrylonitrileYield 65%

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a stirred mixture of 3-(5-isopropyl-2,6-dimethoxy-pyrimidine-4-carbonyl)-5-methyl-benzaldehyde (2.26 g, 6.89 mmol) and diethyl cyanomethylphosphonate (1.14 ml, 7.03 mmol) in anhydrous THF (15 ml) at 0° C. (ice bath) under nitrogen atmosphere, was added potassium t-butoxide (0.85 g, 7.58 mmol). After stirring for 1 hr., the mixture was further stirred for 4 hr. at room temperature. The reaction mixture was diluted with ether, washed with water, dried with anhydrous magnesium sulfate, filtered, and evaporated in vacuo. The residue was purified by silica gel column chromatography (eluent, EA:hexanes (1:4)) to afford 1.56 g (65%) of a white solid. m.p. 144-145° C.; 1H NMR (300 MHz, CDCl3) δ 1.19 (6H, d, J=6.9 Hz), 2.42 (3H, s), 2.83 (1H, m), 3.94 (3H, s), 4.08 (3H, s), 5.92 (1H, d, J=16.8 Hz), 3.39 (1H, d, J=16.8 Hz), 7.49 (1H, s), 7.69 (1H, s), 7.75 (1H, s).

Workup

  1. stirring, the mixture was further stirred for 4 hr
  2. customat room temperature
  3. washwashed with water
  4. dry with materialdried with anhydrous magnesium sulfate
  5. filtrationfiltered
  6. customevaporated in vacuo
  7. customThe residue was purified by silica gel column chromatography (eluent, EA:hexanes (1:4))

Sources & evidence

ORD record
ord-5c2d28c1b1d94074a05b99befeabf966
Source dataset
uspto-grants-2012_01
Patent number
US08106064B2

Reaction notes

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