2-Chlorobenzimidazole → HCID 178472428, compound

HRID 843682Notes

Reaction equation

HRID 843682 reaction equation
Cl[C:2]1[NH:3][C:4]2[CH:10]=[CH:9][CH:8]=[CH:7][C:5]=2[N:6]=1.[CH2:11]([O:13][C:14]([CH:16]1[CH2:21][CH2:20][CH:19]([NH2:22])[CH2:18][CH2:17]1)=[O:15])[CH3:12].C(N(C(C)C)CC)(C)C>CCO>[CH2:11]([O:13][C:14]([C@H:16]1[CH2:21][CH2:20][C@@H:19]([NH:22][C:2]2[NH:3][C:4]3[CH:10]=[CH:9][CH:8]=[CH:7][C:5]=3[N:6]=2)[CH2:18][CH2:17]1)=[O:15])[CH3:12]

Participants

5

Reactant 3

HCID 785722-ChlorobenzimidazoleHCID 81531DiisopropylethylamineHCID 409963Ethyl 4-aminocyclohexanecarboxylate

Product 1

HCID 178472428HCID 178472428, compoundYield 32.2%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Conditions

Temperature
200 °C

Procedure

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) δ 7.28 (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) δ 7.28 (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].

Workup

  1. customwere placed in a glass high pressure tube
  2. customthe reaction vessel was sealed
  3. temperatureto cool to room temperature
  4. temperatureheated
  5. dissolutionto dissolve the reaction mixture
  6. customThe reaction mixture was partitioned between aqueous NaHCO3 and EtOAc
  7. washthe organic layer was washed with water and brine
  8. dry with materialdried over MgSO4
  9. filtrationfiltered
  10. concentrationconcentrated
  11. customPurification of the crude product on silica gel (gradient, 1:1 hexanes:EtOAc to EtOAc)

Sources & evidence

ORD record
ord-a6ec54f650984da389d80eaa6f63a8d3
Source dataset
uspto-grants-2002_04
Patent number
US06380205B1

Reaction notes

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