反応 #1994293

反応方程式

6-amino-5-chloro-2-(4-chloro-2-fluorophenyl)-pyrimidine-4-carboxylic acid

HCl

acetyl chloride

ethyl acetate hexane

→

title compound

収率 63.5%

6-Amino-5-chloro-2-(4-chloro-2-fluorophenyl)pyrimidine-4-carboxylic acid ethyl ester

収率 63.5%

溶媒

ethanol

ethanol

反応条件

後処理

1. 1
   温度cooled in an ice bath
2. 2
   濃縮The reaction mixture was concentrated
3. 3
   その他the residue partitioned between ethyl acetate and water
4. 4
   その他The organic phase was dried
5. 5
   濃縮concentrated
6. 6
   その他the product was purified by column chromatography (dichloromethane/ethyl acetate gradient)

実験手順

A 1N solution of HCl in ethanol was generated by adding 0.565 mL of acetyl chloride dropwise to 12 mL of ethanol cooled in an ice bath. This solution was added to 200 mg of 6-amino-5-chloro-2-(4-chloro-2-fluorophenyl)-pyrimidine-4-carboxylic acid and the resulting solution was heated at 62° C. overnight. The reaction mixture was concentrated and the residue partitioned between ethyl acetate and water. The organic phase was dried and concentrated, and the product was purified by column chromatography (dichloromethane/ethyl acetate gradient). A second chromatography utilizing an amine-functionalized silica gel column (Biotage KP-NH) and an ethyl acetate/hexane gradient solvent system yielded the title compound (139 mg, 63.5% yield): mp 131-132° C.: 1H NMR (CDCl3): δ 7.97 (m, 1H), 7.2 (m, 2H), 5.63 (br s, 2H), 4.48 (q, 2H), 1.44 (t, 3H).

出典