Sodium hydride → 4-(2,6-Difluorobenzyl)-6-(1-methyl-2-butynyloxy)pyrimidine

HRID 1759927

Reaction equation

HRID 1759927 reaction equation
[H-].[Na+].[CH3:3][CH:4]([OH:8])[C:5]#[C:6][CH3:7].Cl[C:10]1[CH:15]=[C:14]([CH2:16][C:17]2[C:22]([F:23])=[CH:21][CH:20]=[CH:19][C:18]=2[F:24])[N:13]=[CH:12][N:11]=1.[Cl-].[NH4+]>O1CCCC1>[F:24][C:18]1[CH:19]=[CH:20][CH:21]=[C:22]([F:23])[C:17]=1[CH2:16][C:14]1[CH:15]=[C:10]([O:8][CH:4]([CH3:3])[C:5]#[C:6][CH3:7])[N:11]=[CH:12][N:13]=1

Participants

6

Reactant 4

HCID 24758Sodium hydrideHCID 25517Ammonium ChlorideHCID 1413443-Pentyn-2-olHCID 225997014-Chloro-6-(2,6-difluorobenzyl)pyrimidine

Product 1

HCID 225998654-(2,6-Difluorobenzyl)-6-(1-methyl-2-butynyloxy)pyrimidineYield 133.6%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Procedure

In 1 ml of tetrahydrofuran was suspended 0.04 g of sodium hydride (60% in oil), to which 0.2 ml of a tetrahydrofuran solution containing 0.06 g of 3-pentyn-2-ol was slowly added dropwise under stirring at room temperature. The mixture was stirred at room temperature for 20 minutes, and 0.4 ml of a tetrahydrofuran solution containing 0.15 g of 4-chloro-6-(2,6-difluorobenzyl)pyrimidine was slowly added dropwise at room temperature, followed by stirring for 3 hours. The reaction mixture was then poured into a saturated aqueous ammonium chloride solution and extracted three times with ethyl acetate. The organic 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-(2,6-difluorobenzyl)-6-(1-methyl-2-butynyloxy)pyrimidine (the present compound (147)).

Workup

  1. additionwas slowly added dropwise
  2. stirringThe mixture was stirred at room temperature for 20 minutes
  3. additionwas slowly added dropwise at room temperature
  4. stirringby stirring for 3 hours
  5. extractionextracted three times with ethyl acetate
  6. washwashed with water
  7. dry with materialdried over anhydrous magnesium sulfate
  8. concentrationconcentrated

Sources & evidence

ORD record
ord-e5a2ccc2f25b4cafb5502ee2c4563a42
Source dataset
uspto-grants-2005_01
Patent number
US06838463B2

Linked notes

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