反応 #554623

反応方程式

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

溶媒

dimethylacetamide

反応条件

後処理

1. 1
   その他to quench all excess NaH
2. 2
   workup.ADDITIONthe mixture poured into 50 ml of 0.5 N HCl
3. 3
   抽出The crude product is extracted with ethyl acetate
4. 4
   洗浄the combined organic phases washed with brine
5. 5
   乾燥dried over MgSO4
6. 6
   その他After evaporation of the solvent
7. 7
   その他the product is purified by flash column chromatography (gradient ethyl acetate:cyclohexane from 1:1 to 3:1)

実験手順

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]+.

出典