反应 #60321

反应方程式

7-fluoro-6-(4-iodo-2-methyl-phenylamino)-(2-trimethylsilanyl-ethoxymethyl)-benzoimidazole-5-carboxylic acid methyl ester

DMF

→

desired product

收率 77.0%

6-(4-Cyano-2-methyl-phenylamino)-7-fluoro-(2-trimethylsilanyl-ethoxymethyl)-benzoimidazole-5-carboxylic acid methyl ester

收率 77.0%

反应条件

后处理

1. 1
   workup.ADDITIONTo a stirred solution of a 1:1 mixture of N1
2. 2
   温度The reaction mixture is cooled to room temperature
3. 3
   其他quenched by the addition of 5 mL of a 4:1:5 mixture of sat NH4Cl
4. 4
   萃取The aqueous layer is extracted with ethyl acetate
5. 5
   洗涤The combined organic extracts are washed with water (3×), brine
6. 6
   干燥dried (MgSO4)
7. 7
   浓缩concentrated under reduced pressure
8. 8
   其他Purification by flash column chromatography
9. 9
   洗涤eluted with 1:1 hexanes

实验过程

To a stirred solution of a 1:1 mixture of N1:N3 isomers of 7-fluoro-6-(4-iodo-2-methyl-phenylamino)-(2-trimethylsilanyl-ethoxymethyl)-benzoimidazole-5-carboxylic acid methyl ester 10jj (0.060 g, 0.108 mmol) in 1 mL DMF at room temperature under N2 is added dppf (2 mg, 0.004 mmol) followed by Pd2 dba3 (2 mg, 0.002 mmol) and Zn(CN)2 (8 mg, 0.065 mmol) (Tetrahedron Lett. 1999, 40, 8193-8195). The reaction mixture is heated to 120° C. for 45 minutes. The reaction mixture is cooled to room temperature and quenched by the addition of 5 mL of a 4:1:5 mixture of sat NH4Cl:conc NH4OH:water. The aqueous layer is extracted with ethyl acetate. The combined organic extracts are washed with water (3×), brine, and dried (MgSO4) and concentrated under reduced pressure. Purification by flash column chromatography eluted with 1:1 hexanes:ethyl acetate provides 38 mg (77%) of desired product as a 1:1 mixture of N1 and N3 isomers: APCI MS (+) m/z 455 (M+1) detected.

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