diethyl (1S,2S)-3,3-dimethylcyclopropane-1,2-dicarboxylate → racemic trans-Ethyl 3-(1-(4-bromobenzyl)-5-(quinolin-2-ylmethoxy)-1H-benzo[d]imidazol-2-yl)-2,2-dimethylcyclopropanecarboxylate

HRID 2178418Notes

Reaction equation

HRID 2178418 reaction equation
C[Al](C)C.[Br:5][C:6]1[CH:32]=[CH:31][C:9]([CH2:10][NH:11][C:12]2[C:13]([NH2:30])=[CH:14][C:15]([O:18][CH2:19][C:20]3[CH:29]=[CH:28][C:27]4[C:22](=[CH:23][CH:24]=[CH:25][CH:26]=4)[N:21]=3)=[CH:16][CH:17]=2)=[CH:8][CH:7]=1.[CH3:33][C:34]1([CH3:47])[C@@H:36]([C:37]([O:39][CH2:40][CH3:41])=[O:38])[C@@H:35]1[C:42](OCC)=O>C(Cl)Cl>[Br:5][C:6]1[CH:32]=[CH:31][C:9]([CH2:10][N:11]2[C:12]3[CH:17]=[CH:16][C:15]([O:18][CH2:19][C:20]4[CH:29]=[CH:28][C:27]5[C:22](=[CH:23][CH:24]=[CH:25][CH:26]=5)[N:21]=4)=[CH:14][C:13]=3[N:30]=[C:42]2[C@H:35]2[C@H:36]([C:37]([O:39][CH2:40][CH3:41])=[O:38])[C:34]2([CH3:33])[CH3:47])=[CH:8][CH:7]=1

Participants

5

Reactant 3

HCID 2724581diethyl (1S,2S)-3,3-dimethylcyclopropane-1,2-dicarboxylateHCID 16682925TrimethylaluminumHCID 90414798N1-(4-bromobenzyl)-4-(quinolin-2-ylmethoxy)benzene-1,2-diamine

Product 1

HCID 117606232racemic trans-Ethyl 3-(1-(4-bromobenzyl)-5-(quinolin-2-ylmethoxy)-1H-benzo[d]imidazol-2-yl)-2,2-dimethylcyclopropanecarboxylate

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
90 °C

Procedure

A solution of trimethyl aluminum (0.2 mL, 2 M in toluene) was added to 25 mL round-bottomed flask containing N1-(4-bromobenzyl)-4-(quinolin-2-ylmethoxy)benzene-1,2-diamine (100 mg, 0.23 mmol), trans-diethyl 3,3-dimethylcyclopropane-1,2-dicarboxylate (49 mg, 0.23 mmol), and DCM (4 mL). After 12 h, the solution was partitioned between sat. NaHCO3 (30 mL) and EtOAc (30 mL). The organic layer was separated and the aqueous layer was extracted with EtOAc (2×30 mL). The combine organic layers were dried with sodium sulfate, filtered, and concentrated to dryness. To the residue was added ethanol (2 mL) and concentrated HCl (0.1 mL, 12 N). The solution heated to 90° C. After 5 h, the mixture was cooled, concentrated to dryness, and purified by reverse phase HPLC to afford the title compound. MS (ESI): mass calcd. for C32H30BrN3O3, 583.15; m/z found, 584.1 [M+H]+.

Workup

  1. customthe solution was partitioned between sat. NaHCO3 (30 mL) and EtOAc (30 mL)
  2. customThe organic layer was separated
  3. extractionthe aqueous layer was extracted with EtOAc (2×30 mL)
  4. dry with materialThe combine organic layers were dried with sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated to dryness
  7. additionTo the residue was added ethanol (2 mL) and concentrated HCl (0.1 mL, 12 N)
  8. waitAfter 5 h
  9. temperaturethe mixture was cooled
  10. concentrationconcentrated to dryness
  11. custompurified by reverse phase HPLC

Sources & evidence

ORD record
ord-6709175c508c4d55b762895798e5ca11
Source dataset
uspto-grants-2015_06
Patent number
US09067917B2

Reaction notes

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