Reaktion #426376

Reaktionsgleichung

sodium hydroxide

5-fluoro-3-iodo-benzene-1,2-diamine

6-fluoro-4-iodo-benzoimidazole-1-carboxylic acid tert-butyl ester

5-fluoro-3-iodo-benzene-1,2-diamine

→

6-fluoro-4-iodo-1H-benzoimidazole

Ausbeute 86.0%

Lösungsmittel

formic acid

Reaktionsbedingungen

Aufarbeitung

1. 1
   Temperaturcooled
2. 2
   TemperaturThe mixture was cooled in an ice bath
3. 3
   Sonstigethe resulting solid was collected
4. 4
   Waschenwashed with water
5. 5
   Sonstigedried in vacuo

Vorschrift

The 6-fluoro-4-iodo-benzoimidazole-1-carboxylic acid tert-butyl ester used in this step was prepared from 5-fluoro-3-iodo-benzene-1,2-diamine according to the procedure of Weber et al., WO 9400124. Briefly, a mixture of 5-fluoro-3-iodo-benzene-1,2-diamine (1.3 grams, 5.16 mmoles) and 1.5 mL of 96% formic acid was stirred at 100° for 3 hours, then cooled, and 35 mL 5% sodium hydroxide was added. The mixture was cooled in an ice bath and the resulting solid was collected, washed with water and dried in vacuo to provide 1.16 grams (86%) 6-fluoro-4-iodo-1H-benzoimidazole, m.p. 210-211° C. A mixture of 1.0 gram (3.8 mmoles) of this benzimidazole, di-tert-butyl dicarbonate (0.92 grams, 4.2 mmole), and 5 mg dimethylaminopyridine in 15 mL dioxane was stirred at 80° C. for 20 hours, then concentrated under reduced pressure. Purification of the residue by column chromatography over silica gel 230-400 mesh eluting with 30% ethyl acetate in hexane gave 6-fluoro-4-iodo-benzoimidazole-1-carboxylic acid tert-butyl ester as a crystalline solid, 1.38 grams (100%), m.p. 73-74° C.

Quelle