2-Chlorobenzimidazole → HCID 178472428, compound

Participants

Reaction Conditions

Reaction Steps

A mixture of 2-Chlorobenzimidazole (I) (0.9 g, 5.9 mmol) and ethyl-4-amino-cyclohexane carboxylate (1.1 g, 5.4 mmol) were placed in a glass high pressure tube. Diisopropylethylamine (2.8 mL, 16.2 mmol) was added, the reaction vessel was sealed and heated to 200° C. for 4 h and allowed to cool to room temperature. Next was added 5 mL EtOH and heated to dissolve the reaction mixture. The reaction mixture was partitioned between aqueous NaHCO3 and EtOAc, and the organic layer was washed with water and brine, dried over MgSO4, filtered and concentrated. Purification of the crude product on silica gel (gradient, 1:1 hexanes:EtOAc to EtOAc) gave the cis 4-(1H-benzimidazol-2-ylamino)-cyclohexanecarboxylic acid ethyl ester (J) (0.5 g) and the trans 4-(1H-benzimidazol-2-ylamino)-cyclohexanecarboxylic acid ethyl ester (K) (0.5 g). Data for (J): 1H NMR (300 MHz, CDCl3) δ7.28 (br s, 2 H), 7.02 (m, 2 H), 5.16 (br s, 1 H), 4.15 (q, 2 H), 3.97 (br s, 1 H), 2.40 (br s, 1 H), 1.80-1.54 (m, 8 H), 1.22 (t, 3 H); mass spectrum m/z 288 [(M+H)+; calcd for C16H22N3O2: 288]. Later fractions gave the trans isomer (K) (0.5 g): 1H NMR (300 MHz, CDCl3) δ7.28 (br s, 2 H), 7.02 (m, 2 H), 4.82 (br s, 1 H), 4.15 (q, 2 H), 3.64 (m, 1 H), 2.20 (br d, 3 H), 1.96 (br d, 2 H), 1.42 (m, 2 H), 1.22 (t, 3 H), 1.20 (m, 2 H); mass spectrum m/z 288 [(M+H)+; calcd for C16H22N3O2: 288].

Provenance & Evidence