Diethyl (cyanomethyl)phosphonate → 3-[3-(5-Isopropyl-2,6-dioxo-1,2,3,6-tetrahydro-pyrimidin-4-yloxy)-5-methyl-phenyl]-acrylonitrile

HRID 426205Notes

Reaction equation

HRID 426205 reaction equation
[CH:1]([C:4]1[C:9](=[O:10])[NH:8][C:7](=[O:11])[NH:6][C:5]=1[O:12][C:13]1[CH:14]=[C:15]([CH:18]=[C:19]([CH3:21])[CH:20]=1)[CH:16]=O)([CH3:3])[CH3:2].[C:22]([CH2:24]P(=O)(OCC)OCC)#[N:23].CC(C)([O-])C.[K+]>C1COCC1.CC(=O)OCC>[CH:1]([C:4]1[C:9](=[O:10])[NH:8][C:7](=[O:11])[NH:6][C:5]=1[O:12][C:13]1[CH:14]=[C:15]([CH:16]=[CH:24][C:22]#[N:23])[CH:18]=[C:19]([CH3:21])[CH:20]=1)([CH3:3])[CH3:2]

Participants

6

Reactant 3

HCID 75676Diethyl (cyanomethyl)phosphonateHCID 23665647Potassium tert-butoxideHCID 591848043-(5-Isopropyl-2,6-dioxo-1,2,3,6-tetrahydro-pyrimidin-4-yloxy)-5-methyl-benzaldehyde

Product 1

HCID 667053313-[3-(5-Isopropyl-2,6-dioxo-1,2,3,6-tetrahydro-pyrimidin-4-yloxy)-5-methyl-phenyl]-acrylonitrileYield 40%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a stirred mixture of 3-(5-isopropyl-2,6-dioxo-1,2,3,6-tetrahydro-pyrimidin-4-yloxy)-5-methyl-benzaldehyde (788 mg, 2.73 mmol) and diethyl cyanomethyl-phosphonate (451 μl, 2.79 mmol) in THF (15 ml) at 0° C. (ice bath) under nitrogen atmosphere, was added potassium t-butoxide (920 mg, 8.2 mmol). After stirring for 1 hr., the mixture was stirred for overnight at room temperature. The mixture was then diluted with EA, washed with aqueous saturated ammonium chloride solution, dried with anhydrous magnesium sulfate, filtered, and evaporated in vacuo. The residue was purified by silica gel column chromatography (eluent, EA: hexanes (from 2:3 to 1:1)) to afford 340 mg (40%) of a white solid. m.p. 279-280° C.; 1H NMR (200 MHz, DMSO-d6) δ 1.05 (6H, d, J=7.0 Hz), 2.33 (3H, s), 2.78 (1H, m), 6.55 (1H, d, J=16.8 Hz), 7.03 (1H, s), 7.21 (1H, s), 7.25 (1H, s), 7.62 (1H, d, J=16.8 Hz), 11.05 (1H, s), 11.31 (1H, s); m/z (LC/Mass, EI) 312 (M+H+).

Workup

  1. stirring, the mixture was stirred for overnight at room temperature
  2. washwashed with aqueous saturated ammonium chloride solution
  3. dry with materialdried with anhydrous magnesium sulfate
  4. filtrationfiltered
  5. customevaporated in vacuo
  6. customThe residue was purified by silica gel column chromatography (eluent, EA: hexanes (from 2:3 to 1:1))

Sources & evidence

ORD record
ord-7c44d2027ac443f48f09c0c3ee48756a
Source dataset
uspto-grants-2012_01
Patent number
US08106064B2

Reaction notes

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