반응 #1994293

반응 방정식

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

HCl

acetyl chloride

ethyl acetate hexane

→

title compound

수율 63.5%

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

수율 63.5%

용매

ethanol

ethanol

반응 조건

후처리

1. 1
   온도cooled in an ice bath
2. 2
   농축The reaction mixture was concentrated
3. 3
   기타the residue partitioned between ethyl acetate and water
4. 4
   기타The organic phase was dried
5. 5
   농축concentrated
6. 6
   기타the product was purified by column chromatography (dichloromethane/ethyl acetate gradient)

실험 절차

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).

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