Reaction #554623

Reaction equation

Water

NaH

2,2,2-Trifluoro-N-(4-hydroxymethyl-benzyl)-acetamide

2-Chloropyrimidin-4-amine

→

N-(4-((4-Aminopyrimidin-2-yloxy)methyl)benzyl)-2,2,2-trifluoroacetamide

Solvents

dimethylacetamide

Conditions

Workup

1. 1
   Otherto quench all excess NaH
2. 2
   workup.ADDITIONthe mixture poured into 50 ml of 0.5 N HCl
3. 3
   ExtractionThe crude product is extracted with ethyl acetate
4. 4
   Washthe combined organic phases washed with brine
5. 5
   Dryingdried over MgSO4
6. 6
   OtherAfter evaporation of the solvent
7. 7
   Otherthe product is purified by flash column chromatography (gradient ethyl acetate:cyclohexane from 1:1 to 3:1)

Procedure

760 mg (3.25 mmol) 2,2,2-Trifluoro-N-(4-hydroxymethyl-benzyl)-acetamide is dissolved in 3 mL dry dimethylacetamide under argon atmosphere, and 273 mg (8.15 mmol) NaH is added over 5 min. 211 mg (1.63 mmol) 2-Chloropyrimidin-4-amine is then added and the solution stirred at 90° C. over night. 1 mL Water is added carefully to quench all excess NaH, and the mixture poured into 50 ml of 0.5 N HCl. The crude product is extracted with ethyl acetate, the combined organic phases washed with brine and dried over MgSO4. After evaporation of the solvent, the product is purified by flash column chromatography (gradient ethyl acetate:cyclohexane from 1:1 to 3:1). Yield: 350 mg (52%). ESI-MS m/z 327 [M+H]+.

Source