反应详情

Sodium cyanide (1.79 9), dissolved in water (5.6 cc) is added dropwise to a mixture, cooled to 0° C., of bromine (5.8 9) and water (5.6 cc). After 1 hour's contact at 0° C., a solution of 4-trifluoromethoxy-1,2-benzenediamine (7 g) in tetrachloroethane (7 cc) is added dropwise. After 2 hours at 0° C., the reaction mixture is poured into water (500 cc). Dichloromethane (500 cc) is added and the mixture is stirred for 20 minutes. After settling has taken place, the aqueous phase is separated and washed with dichloromethane (2×150 cc) and alkalinized to pH 8 with sodium carbonate. The base is extracted with ethyl acetate (3×300 cc) and the organic phase is dried over magnesium sulphate and evaporated under reduced pressure. Crude base (9.5 g) is obtained, which is purified by preparative HPLC using a dichloromethane/ethanol mixture (95:5 by volume) as eluent. An oil is recovered, which is converted to a hydrochloride in ethyl ether. 5-Trifluoromethoxy-2-benzimidazolamine hydrochloride (4.8 g), m.p. 180° C., is obtained.

1. additionis added dropwise to a mixture
2. waitAfter 2 hours at 0° C.
3. customthe aqueous phase is separated
4. washwashed with dichloromethane (2×150 cc)
5. extractionThe base is extracted with ethyl acetate (3×300 cc)
6. dry with materialthe organic phase is dried over magnesium sulphate
7. customevaporated under reduced pressure
8. customCrude base (9.5 g) is obtained
9. customwhich is purified by preparative HPLC
10. customAn oil is recovered