Hydrochloric Acid → Cyclohexyl-[5,6-difluoro-2-((S)-methoxy-phenyl-methyl)-benzoimidazol-1-yl]-acetic acid

HRID 1099466Notes

Reaction equation

HRID 1099466 reaction equation
C(N[C:9](=[O:37])[CH:10]([CH:31]1[CH2:36][CH2:35][CH2:34][CH2:33][CH2:32]1)[N:11]1[C:15]2[CH:16]=[C:17]([F:21])[C:18]([F:20])=[CH:19][C:14]=2[N:13]=[C:12]1[C@@H:22]([O:29][CH3:30])[C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1)C1C=CC=CC=1.C([O:42]C(OC(OC(C)(C)C)=O)=O)(C)(C)C.O.[OH-].[Li+].Cl>C(#N)C.O>[CH:31]1([CH:10]([N:11]2[C:15]3[CH:16]=[C:17]([F:21])[C:18]([F:20])=[CH:19][C:14]=3[N:13]=[C:12]2[C@@H:22]([O:29][CH3:30])[C:23]2[CH:24]=[CH:25][CH:26]=[CH:27][CH:28]=2)[C:9]([OH:42])=[O:37])[CH2:36][CH2:35][CH2:34][CH2:33][CH2:32]1

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 90495Di-tert-butyl dicarbonateHCID 168937Lithium hydroxide, monohydrateHCID 66810470N-Benzyl-2-cyclohexyl-2-[5,6-difluoro-2-((S)-methoxy-phenyl-methyl)-benzoimidazol-1-yl]-acetamide

Product 1

HCID 66810386Cyclohexyl-[5,6-difluoro-2-((S)-methoxy-phenyl-methyl)-benzoimidazol-1-yl]-acetic acid

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6342AcetonitrileSolvent

Procedure

To a solution of N-benzyl-2-cyclohexyl-2-[5,6-difluoro-2-((S)-methoxy-phenyl-methyl)-benzoimidazol-1-yl]-acetamide (2.16 g, 4 mmol, 1.0 equiv) in acetonitrile (25 ml) were added di-tert.-butyl-dicarbonate (1.123 g, 5 mmol, 1.2 equiv., [CAS RN 24424-99-5]) and N,N-dimethylaminopyridine ((0.051 g, 0.1 equiv., [CAS RN 1122-58-3]). The mixture was stirred 48 h at room temperature. A solution of lithium hydroxide monohydrate (0.54 g, 3.0 equiv., [CAS RN 1310-66-3]) in water (4 ml) was added, and the mixture vigorously stirred overnight at room temperature, and 2 h at 70° C. The mixture was allowed to cool to room temperature and poured into 1M aqueous hydrochloric acid (25 ml). The product was extracted with ethyl acetate (3×50 ml) and the combined organic phases washed with brine and dried over magnesium sulfate. The brown residue was purified by column chromatography on silica gel (75 g, 1:0 to 98:2 EtOAc/AcOH eluant) to afford the product as an off-white mixture of diastereomers. MS (ISN): 413.1 [M−H]−.

Workup

  1. customthe mixture vigorously stirred overnight
  2. customat room temperature
  3. custom2 h
  4. customat 70° C
  5. temperatureto cool to room temperature
  6. extractionThe product was extracted with ethyl acetate (3×50 ml)
  7. washthe combined organic phases washed with brine
  8. dry with materialdried over magnesium sulfate
  9. customThe brown residue was purified by column chromatography on silica gel (75 g, 1:0 to 98:2 EtOAc/AcOH eluant)
  10. customto afford the product
  11. additionas an off-white mixture of diastereomers

Sources & evidence

ORD record
ord-29f92dd9b4bd4e15af914e6afe67d109
Source dataset
uspto-grants-2012_03
Patent number
US08143422B2

Reaction notes

Loading…