Sodium hydride → 4-Chloro-5-fluoro-6-(2-pentynyloxy)pyrimidine

HRID 2425919Notes

Reaction equation

HRID 2425919 reaction equation
[H-].[Na+].[CH2:3]([OH:8])[C:4]#[C:5][CH2:6][CH3:7].[Cl:9][C:10]1[C:15]([F:16])=[C:14](Cl)[N:13]=[CH:12][N:11]=1.[Cl-].[NH4+]>O1CCCC1>[Cl:9][C:10]1[C:15]([F:16])=[C:14]([O:8][CH2:3][C:4]#[C:5][CH2:6][CH3:7])[N:13]=[CH:12][N:11]=1

Participants

6

Reactant 4

HCID 24758Sodium hydrideHCID 25517Ammonium ChlorideHCID 804212-Pentyn-1-olHCID 112866754,6-Dichloro-5-fluoropyrimidine

Product 1

HCID 593411204-Chloro-5-fluoro-6-(2-pentynyloxy)pyrimidineYield 102.9%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Procedure

0.58 g of sodium hydride (60% oil suspension) was suspended in 20 ml of tetrahydrofuran. 1 ml of tetrahydrofuran solution of 0.88 g of 2-pentyn-1-ol was added dropwise at 0° C. therein slowly, and the mixture was stirred for 10 minutes. Into the mixture was added dropwise 5 ml of tetrahydrofuran solution of 2 g of 4,6-dichloro-5-fluoropyrimidine at 0° C., and stirred for 70 minutes. The reaction mixture was poured into a saturated ammonium chloride aqueous solution, and the mixture was extracted with tert-butyl methyl ether three times. The organic layers were washed with water, dried over anhydrous magnesium sulfate and concentrated. The residue was subjected to silica gel column chromatography to obtain 2.31 g of 4-chloro-5-fluoro-6-(2-pentynyloxy)pyrimidine.

Workup

  1. stirringstirred for 70 minutes
  2. extractionthe mixture was extracted with tert-butyl methyl ether three times
  3. washThe organic layers were washed with water
  4. dry with materialdried over anhydrous magnesium sulfate
  5. concentrationconcentrated

Sources & evidence

ORD record
ord-4b772cde1919484b81dd54ed7e0e72fa
Source dataset
uspto-grants-2011_06
Patent number
US07968537B2

Reaction notes

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