2-Butyn-1-ol → 4-(2-Butynyloxy)-6-(2-chloro-5-methyl-6-fluorobenzyl)pyrimidine

HRID 1592187Notes

Reaction equation

HRID 1592187 reaction equation
[H-].[Na+].[CH2:3]([OH:7])[C:4]#[C:5][CH3:6].Cl[C:9]1[CH:14]=[C:13]([CH2:15][C:16]2[C:21]([F:22])=[C:20]([CH3:23])[CH:19]=[CH:18][C:17]=2[Cl:24])[N:12]=[CH:11][N:10]=1.[Cl-].[NH4+]>O1CCCC1>[CH2:3]([O:7][C:9]1[CH:14]=[C:13]([CH2:15][C:16]2[C:21]([F:22])=[C:20]([CH3:23])[CH:19]=[CH:18][C:17]=2[Cl:24])[N:12]=[CH:11][N:10]=1)[C:4]#[C:5][CH3:6]

Participants

6

Reactant 4

HCID 129912-Butyn-1-olHCID 24758Sodium hydrideHCID 25517Ammonium ChlorideHCID 225996724-Chloro-6-(2-chloro-5-methyl-6-fluorobenzyl)pyrimidine

Product 1

HCID 225996884-(2-Butynyloxy)-6-(2-chloro-5-methyl-6-fluorobenzyl)pyrimidineYield 106.8%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Procedure

In 2 ml of tetrahydrofuran was suspended 0.04 g of sodium hydride (60% in oil), to which 0.6 ml of a tetrahydrofuran solution containing 0.06 g of 2-butyn-1-ol was slowly added dropwise with stirring at room temperature. The mixture was then stirred at room temperature for 20 minutes, to which 0.6 ml of a tetrahydrofuran solution containing 0.2 g of 4-chloro-6-(2-chloro-5-methyl-6-fluorobenzyl)pyrimidine was slowly added dropwise at room temperature, followed by stirring for 4 hours. The reaction mixture was then poured into a saturated aqueous ammonium chloride solution and extracted three times with chloroform. The chloroform layers were combined, washed with water, dried over anhydrous magnesium sulfate, and then concentrated. The residue was subjected to silica gel column chromatography to give 0.24 g of 4-(2-butynyloxy)-6-(2-chloro-5-methyl-6-fluorobenzyl)pyrimidine (the present compound (121)).

Workup

  1. additionwas slowly added dropwise
  2. additionwas slowly added dropwise at room temperature
  3. stirringby stirring for 4 hours
  4. extractionextracted three times with chloroform
  5. washwashed with water
  6. dry with materialdried over anhydrous magnesium sulfate
  7. concentrationconcentrated

Sources & evidence

ORD record
ord-09b21f20d6374f3bb93da580a8c12691
Source dataset
uspto-grants-2007_11
Patent number
US07291730B2

Reaction notes

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