반응 #60257

반응 방정식

6-(2-Chloro-phenylamino)-7-fluoro-3H-benzoimidazole-5carboxylic acid methyl ester

6-(2-Chloro-phenylamino)-7-fluoro-3H-benzoimidazole-5-carboxylic acid methyl ester

TsOH.H2O

NBS

→

pure desired product

수율 85.0%

6-(4-Bromo-2-chloro-phenylamino)-7-fluoro-3H-benzoimidazole-5-carboxylic acid methyl ester

수율 85.0%

용매

THF MeOH

반응 조건

후처리

1. 1
   온도cooled to −780C under an atmosphere of nitrogen
2. 2
   온도2 hours later warmed to room temperature
3. 3
   workup.WAITAfter 16 hours
4. 4
   기타the reaction mixture is quenched by the addition of 10% Na2S2O3
5. 5
   workup.ADDITIONdiluted with ethyl acetate and water
6. 6
   기타The layers are separated
7. 7
   추출the aqueous layer is extracted with ethyl acetate
8. 8
   건조The combined organic extracts are dried (MgSO4)
9. 9
   농축concentrated under reduced pressure
10. 10
    기타The crude product is triturated with methylene chloride

실험 절차

6-(2-Chloro-phenylamino)-7-fluoro-3H-benzoimidazole-5carboxylic acid methyl ester 7b (55 mg, 0.172 mmol) is dissolved in 1:1 THF/MeOH (2 mL) and cooled to −780C under an atmosphere of nitrogen. TsOH.H2O (49 mg, 0.258 mmol) is added followed by NBS (31 mg, 0.174 mmol). After 10 minutes, the reaction mixture is warmed to 0° C. and then 2 hours later warmed to room temperature. After 16 hours, the reaction mixture is quenched by the addition of 10% Na2S2O3 and diluted with ethyl acetate and water. The layers are separated and the aqueous layer is extracted with ethyl acetate. The combined organic extracts are dried (MgSO4) and concentrated under reduced pressure. The crude product is triturated with methylene chloride to give 58 mg (85%) of pure desired product as a tan solid.

출처