Diethyl (cyanomethyl)phosphonate → 3-{3-[5-Isopropyl-2,6-bis-(4-methoxy-benzyloxy)-pyrimidine-4-carbonyl]-phenyl}-acrylonitrile

HRID 426194Notes

Reaction equation

HRID 426194 reaction equation
[CH:1]([C:4]1[C:5]([C:30]([C:32]2[CH:33]=[C:34]([CH:37]=[CH:38][CH:39]=2)[CH:35]=O)=[O:31])=[N:6][C:7]([O:20][CH2:21][C:22]2[CH:27]=[CH:26][C:25]([O:28][CH3:29])=[CH:24][CH:23]=2)=[N:8][C:9]=1[O:10][CH2:11][C:12]1[CH:17]=[CH:16][C:15]([O:18][CH3:19])=[CH:14][CH:13]=1)([CH3:3])[CH3:2].[C:40]([CH2:42]P(=O)(OCC)OCC)#[N:41].CC(C)([O-])C.[K+]>C1COCC1>[CH:1]([C:4]1[C:5]([C:30]([C:32]2[CH:33]=[C:34]([CH:35]=[CH:42][C:40]#[N:41])[CH:37]=[CH:38][CH:39]=2)=[O:31])=[N:6][C:7]([O:20][CH2:21][C:22]2[CH:27]=[CH:26][C:25]([O:28][CH3:29])=[CH:24][CH:23]=2)=[N:8][C:9]=1[O:10][CH2:11][C:12]1[CH:17]=[CH:16][C:15]([O:18][CH3:19])=[CH:14][CH:13]=1)([CH3:3])[CH3:2]

Participants

5

Reactant 3

HCID 75676Diethyl (cyanomethyl)phosphonateHCID 23665647Potassium tert-butoxideHCID 591848203-[5-Isopropyl-2,6-bis-(4-methoxy-benzyloxy)-pyrimidine-4-carbonyl]-benzaldehyde

Product 1

HCID 667055543-{3-[5-Isopropyl-2,6-bis-(4-methoxy-benzyloxy)-pyrimidine-4-carbonyl]-phenyl}-acrylonitrileYield 82.5%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a stirred mixture of 3-[5-isopropyl-2,6-bis-(4-methoxy-benzyloxy)-pyrimidine-4-carbonyl]-benzaldehyde (1.73 g, 3.22 mmol) and diethyl cyanomethylphosphonate (0.52 ml, 3.22 mmol) in anhydrous THF (10 ml) at 0° C. (ice bath) under nitrogen atmosphere, was added potassium t-butoxide (397 mg, 3.54 mmol). After 1 hr., the mixture was stirred for overnight at room temperature. 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 (2:7)) to afford 1.46 g (81%) of a pale yellow syrup. 1H NMR (200 MHz, CDCl3) δ 1.19 (6H, d, J=7.0 Hz), 2.86 (1H, m), 3.82 (3H, s), 3.85 (3H, s), 5.31 (2H, s), 5.46 (2H, s), 5.93 (1H, d J=16.8 Hz), 6.81-6.97 (4H, m), 7.28-7.93 (8H, m).

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 (2:7))

Sources & evidence

ORD record
ord-f266da35b36642dd8ea92c417cf9ff4e
Source dataset
uspto-grants-2012_01
Patent number
US08106064B2

Reaction notes

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