Sodium Iodide → Ethyl[3-[(4-chlorophenyl)methyl]-2-(1,1-dimethylethyl)-3,4,5,6,7,8-hexahydrocyclohepta[d]imidazol-4-yl]acetate

HRID 1946482Notes

Reaction equation

HRID 1946482 reaction equation
C[Si](Cl)(C)C.[I-].[Na+].[Cl:8][C:9]1[CH:14]=[CH:13][C:12]([CH2:15][N:16]2[C:20]3[C:21]([CH2:27][C:28]([O:30][CH2:31][CH3:32])=[O:29])(O)[CH2:22][CH2:23][CH2:24][CH2:25][C:19]=3[N:18]=[C:17]2[C:33]([CH3:36])([CH3:35])[CH3:34])=[CH:11][CH:10]=1>C(#N)C>[Cl:8][C:9]1[CH:10]=[CH:11][C:12]([CH2:15][N:16]2[C:20]3[CH:21]([CH2:27][C:28]([O:30][CH2:31][CH3:32])=[O:29])[CH2:22][CH2:23][CH2:24][CH2:25][C:19]=3[N:18]=[C:17]2[C:33]([CH3:34])([CH3:36])[CH3:35])=[CH:13][CH:14]=1

Participants

5

Reactant 3

HCID 5238Sodium IodideHCID 6397ChlorotrimethylsilaneHCID 58460200Ethyl [3-[(4-chlorophenyl)methyl]-2-(1,1-dimethylethyl)-4-hydroxy-3,4,5,6,7,8-hexahydrocyclohepta[d]imidazol-4-yl]acetate

Product 1

HCID 58460191Ethyl[3-[(4-chlorophenyl)methyl]-2-(1,1-dimethylethyl)-3,4,5,6,7,8-hexahydrocyclohepta[d]imidazol-4-yl]acetateYield 5.4%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent2×

Procedure

A mixture of TMSCl (0.513 mL), sodium iodide (601 mg) and acetonitrile (9 ml) was added to a stirred suspension of Intermediate 15 (420 mg) in acetonitrile (3 ml). The RM was stirred at room temp under nitrogen overnight. The reaction mixture was partitioned between EtOAc (50 ml) and sat. NaHCO3 aq. sol.: water (1:1, 50 ml). The two phases were separated and the aqueous phase was extracted again with EtOAc (50 ml). The phases were separated; the organic extracts were combined, dried (hydrophobic frit) and concentrated under vacuum. The residue was purified by reverse phase chromatography using an acetonitrile—0.1% NH3:water—with an amonium carbonate buffer modifier (pH=10) 5%-35% gradient. The desired fractions were combined and concentrated under vacuum. The mixture was purified by MDAP (Method B). The desired fractions were combined and concentrated under nitrogen blowdown to give the title compound (22 mg). LC/MS MH+ 403 Rt 1.09 min (2 minute run).

Workup

  1. customThe reaction mixture was partitioned between EtOAc (50 ml) and sat. NaHCO3 aq. sol.
  2. customThe two phases were separated
  3. extractionthe aqueous phase was extracted again with EtOAc (50 ml)
  4. customThe phases were separated
  5. customdried (hydrophobic frit)
  6. concentrationconcentrated under vacuum
  7. customThe residue was purified by reverse phase chromatography
  8. concentrationconcentrated under vacuum
  9. customThe mixture was purified by MDAP (Method B)
  10. concentrationconcentrated under nitrogen

Sources & evidence

ORD record
ord-e82b9fa59ff14eb893bdfa95ef0ccfb7
Source dataset
uspto-grants-2013_03
Patent number
US08399444B2

Reaction notes

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