Sodium hydride → HCID 59686842, compound

HRID 1804692Notes

Reaction equation

HRID 1804692 reaction equation
[CH2:1]([O:8][C:9]1[N:14]=[C:13]([O:15][CH2:16][C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)[C:12]([CH:23]([CH3:25])[CH3:24])=[C:11](Cl)[N:10]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[C:27]([CH2:29][C:30]1[CH:31]=[C:32]([CH:35]=[C:36]([CH3:38])[CH:37]=1)[C:33]#[N:34])#[N:28].[H-].[Na+].[Cl-].[NH4+]>CN(C=O)C>[CH2:1]([O:8][C:9]1[N:10]=[C:11]([CH:29]([C:27]#[N:28])[C:30]2[CH:31]=[C:32]([CH:35]=[C:36]([CH3:38])[CH:37]=2)[C:33]#[N:34])[C:12]([CH:23]([CH3:25])[CH3:24])=[C:13]([O:15][CH2:16][C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)[N:14]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

6

Reactant 4

HCID 24758Sodium hydrideHCID 25517Ammonium ChlorideHCID 59686861HCID 59686861, compoundHCID 667054463-(Cyanomethyl)-5-methylbenzonitrile

Product 1

HCID 59686842HCID 59686842, compoundYield 94%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

2,4-bis(benzyloxy)-6-chloro-5-isopropylpyrimidine (45.4 g, 0.123 M) and 3-(cyanomethyl)-5-methylbenzonitrile (18.3 g, 0.117 M) were dissolved in anhydrous DMF (200 mL). After cooling the mixture in an ice bath under nitrogen atmosphere, 60% sodium hydride (9.38 g, 0.235 M) was added portionwise (addition time ca. 1.5 hr.). The mixture was stirred for further 1 hr. in an ice bath and stirred for ca. 20 hr. at room temperature. The reaction mixture was then cooled in an ice bath and sat. aqueous ammonium chloride solution was added thoroughly. The crude product was extracted with ether, washed with water twice, dried with magnesium sulfate, filtered, and evaporated in vacuo to give a light brown syrup, which was purified by silica gel column chromatography (eluent, ethyl acetate:hexane (1:9)) to afford 53.46 g (94%) of 3-((2,6-bis(benzyloxy)-5-isopropylpyrimidin-4-yl) (cyano)methyl)-5-methylbenzonitrile as a light brown syrup. λmax (film) 2236 (nitrile) cm−1, 1H NMR (200 MHz, CDCl3) δ 1.10 (3H, d, J=6.9 Hz), 1.12 (3H, d, J=6.9 Hz), 2.36 (3H, s), 2.96 (1H, m), 5.37 (1H, s), 5.44 (4H, s), 7.32-7.55 (13H, m).

Workup

  1. temperatureAfter cooling the mixture in an ice bath under nitrogen atmosphere
  2. addition(addition time ca. 1.5 hr.)
  3. stirringin an ice bath and stirred for ca. 20 hr
  4. customat room temperature
  5. temperatureThe reaction mixture was then cooled in an ice bath
  6. extractionThe crude product was extracted with ether
  7. washwashed with water twice
  8. dry with materialdried with magnesium sulfate
  9. filtrationfiltered
  10. customevaporated in vacuo
  11. customto give a light brown syrup, which
  12. customwas purified by silica gel column chromatography (eluent, ethyl acetate:hexane (1:9))

Sources & evidence

ORD record
ord-5a3934e4b073471a9ff71b16ef41ee43
Source dataset
uspto-grants-2013_01
Patent number
US08354421B2

Reaction notes

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