반응 #60276

반응 방정식

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

potassium carbonate

→

product

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

용매

N,N-dimethylformamide

ethyl acetate

water

반응 조건

후처리

1. 1
   workup.ADDITIONThe reaction mixture is poured into a separatory funnel
2. 2
   기타the layers separated
3. 3
   세척The ethyl acetate layer is washed with water and brine
4. 4
   건조dried (Na2SO4)
5. 5
   농축concentrated under reduced pressure
6. 6
   기타The resulting solid residue is triturated with diethyl ether
7. 7
   기타to yield a pale yellow solid (N3 regioisomer by NMR)
8. 8
   workup.ADDITIONa yellow filtrate (mixture of N1 and N3 regioisomers by NMR)
9. 9
   기타The solids are collected
10. 10
    세척washed with diethyl ether

실험 절차

6-(4-Bromo-2-chloro-phenylamino)-7-fluoro-3H-benzoimidazole-5-carboxylic acid methyl ester 8b (0.25 g, 0.63 mmol) is dissolved in N,N-dimethylformamide (5 mL). 2-Brothomethyl-tetrahydro-pyran (0.34 g, 1.88 mmol) and potassium carbonate (0.26 g, 1.88 mmol) are added and the reaction mixture is stirred at 60° C. for 12 hours under N2. The reaction mixture is poured into a separatory funnel, diluted with ethyl acetate and water and the layers separated. The ethyl acetate layer is washed with water and brine, dried (Na2SO4) and concentrated under reduced pressure. The resulting solid residue is triturated with diethyl ether to yield a pale yellow solid (N3 regioisomer by NMR) and a yellow filtrate (mixture of N1 and N3 regioisomers by NMR). The solids are collected and washed with diethyl ether to yield 0.12 g (37%) of the pure desired N3 regioisomeric product as a pale yellow solid. MS ESI (+) m/z 496, 498 (M+, Br pattern) detected.

출처