Lithium hydroxide, monohydrate → 3-(3-{3-(3-Bromo-benzyl)-2-[tert-butoxycarbonylimino]-2,3-dihydro-benzoimidazol-1-yl}-propoxy)-benzoic acid

HRID 410369Notes

Reaction equation

HRID 410369 reaction equation
C([O:3][C:4](=[O:40])[C:5]1[CH:10]=[CH:9][CH:8]=[C:7]([O:11][CH2:12][CH2:13][CH2:14][N:15]2[C:19]3[CH:20]=[CH:21][CH:22]=[CH:23][C:18]=3[N:17]([CH2:24][C:25]3[CH:30]=[CH:29][CH:28]=[C:27]([Br:31])[CH:26]=3)[C:16]2=[N:32][C:33]([O:35][C:36]([CH3:39])([CH3:38])[CH3:37])=[O:34])[CH:6]=1)C.O[Li].O>C1COCC1.CO.O>[Br:31][C:27]1[CH:26]=[C:25]([CH:30]=[CH:29][CH:28]=1)[CH2:24][N:17]1[C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][C:19]=2[N:15]([CH2:14][CH2:13][CH2:12][O:11][C:7]2[CH:6]=[C:5]([CH:10]=[CH:9][CH:8]=2)[C:4]([OH:40])=[O:3])[C:16]1=[N:32][C:33]([O:35][C:36]([CH3:38])([CH3:39])[CH3:37])=[O:34]

Participants

6

Reactant 2

HCID 168937Lithium hydroxide, monohydrateHCID 674286753-(3-{3-(3-Bromo-benzyl)-2-[tert-butoxycarbonylimino]-2,3-dihydro-benzoimidazol-1-yl}-propoxy)-benzoic acid ethyl ester

Product 1

HCID 674283863-(3-{3-(3-Bromo-benzyl)-2-[tert-butoxycarbonylimino]-2,3-dihydro-benzoimidazol-1-yl}-propoxy)-benzoic acidYield 103.4%

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
40 °C

Procedure

To a solution of 3-(3-{3-(3-bromo-benzyl)-2-[tert-butoxycarbonylimino]-2,3-dihydro-benzoimidazol-1-yl}-propoxy)-benzoic acid ethyl ester (155 mg, 0.25 mmol) in THF (2 ml), MeOH (2 ml) and H2O (1 ml) was added LiOH.H2O (53 mg, 1.27 mmol). The reaction was warmed to 40° C. where it was maintained for 20 h. After this time, the reaction was cooled to rt concentrated under reduced pressure and then partitioned between EtOAc and 1M HCl. The organic phase was separated and the aqueous phase was extracted with additional EtOAc. The combined organic layers were washed with brine, dried (Na2SO4), filtered and concentrated under reduced pressure to provide 3-(3-{3-(3-bromo-benzyl)-2-[tert-butoxycarbonylimino]-2,3-dihydro-benzoimidazol-1-yl}-propoxy)-benzoic acid (150 mg, 100%). HPLC-MS 580, 582 [M+1]+.

Workup

  1. temperaturewas maintained for 20 h
  2. temperatureAfter this time, the reaction was cooled to rt
  3. concentrationconcentrated under reduced pressure
  4. custompartitioned between EtOAc and 1M HCl
  5. customThe organic phase was separated
  6. extractionthe aqueous phase was extracted with additional EtOAc
  7. washThe combined organic layers were washed with brine
  8. dry with materialdried (Na2SO4)
  9. filtrationfiltered
  10. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-4bfacc3b32ef41378d4a87be41190ae0
Source dataset
uspto-grants-2014_06
Patent number
US08759520B2

Reaction notes

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