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

HRID 1946470Notes

Reaction equation

HRID 1946470 reaction equation
[I-].[Na+].[Cl:3][C:4]1[CH:9]=[CH:8][C:7]([CH2:10][N:11]2[C:15]3[C:16]([CH2:22][C:23]([O:25][CH2:26][CH3:27])=[O:24])(O)[CH2:17][CH2:18][CH2:19][CH2:20][C:14]=3[N:13]=[C:12]2[CH:28]([CH3:30])[CH3:29])=[CH:6][CH:5]=1>C(#N)C>[Cl:3][C:4]1[CH:5]=[CH:6][C:7]([CH2:10][N:11]2[C:15]3[CH:16]([CH2:22][C:23]([O:25][CH2:26][CH3:27])=[O:24])[CH2:17][CH2:18][CH2:19][CH2:20][C:14]=3[N:13]=[C:12]2[CH:28]([CH3:29])[CH3:30])=[CH:8][CH:9]=1

Participants

4

Reactant 2

HCID 5238Sodium IodideHCID 58460233Ethyl [3-[(4-chlorophenyl)methyl]-4-hydroxy-2-(1-methylethyl)-3,4,5,6,7,8-hexahydrocyclohepta[d]imidazol-4-yl]acetate

Product 1

HCID 58460173Ethyl [3-[(4-chlorophenyl)methyl]-2-(1-methylethyl)-3,4,5,6,7,8-hexahydrocyclohepta[d]imidazol-4-yl]acetateYield 14.6%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent2×

Conditions

Temperature
-6 °C

Procedure

A mixture of TMSCI (0.846 mL) and sodium iodide (992 mg) in acetonitrile (12 ml) was added dropwise to a stirred suspension of Intermediate 4 (670 mg) in acetonitrile, cooled to −6° C. and keeping the temperature under 0° C. The RM was stirred at −6° C. and gradually warmed up to room temp 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 on silica using a cyclohexane:ethyl acetate 0-100% gradient. The desired fractions were combined and concentrated under vacuum to give the title compound (94 mg). LC/MS MH+ 389, Rt 1.32 min (2 minute run).

Workup

  1. customunder 0° C
  2. temperaturegradually warmed up to room temp overnight
  3. customThe reaction mixture was partitioned between EtOAc (50 ml)
  4. customThe two phases were separated
  5. extractionthe aqueous phase was extracted again with EtOAc (50 ml)
  6. customThe phases were separated
  7. customdried (hydrophobic frit)
  8. concentrationconcentrated under vacuum
  9. customThe residue was purified on silica using a cyclohexane
  10. concentrationconcentrated under vacuum

Sources & evidence

ORD record
ord-d859b6bc59544d00b548c88f8427b569
Source dataset
uspto-grants-2013_03
Patent number
US08399444B2

Reaction notes

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