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

HRID 1946481Notes

Reaction equation

HRID 1946481 reaction equation
[C:1]([O:4][CH2:5][CH3:6])(=[O:3])[CH3:2].[Li+].C[Si]([N-][Si](C)(C)C)(C)C.[Cl:17][C:18]1[CH:23]=[CH:22][C:21]([CH2:24][N:25]2[C:29]3[C:30](=[O:35])[CH2:31][CH2:32][CH2:33][CH2:34][C:28]=3[N:27]=[C:26]2[C:36]([CH3:39])([CH3:38])[CH3:37])=[CH:20][CH:19]=1.[NH4+].[Cl-]>C1COCC1>[Cl:17][C:18]1[CH:19]=[CH:20][C:21]([CH2:24][N:25]2[C:29]3[C:30]([CH2:2][C:1]([O:4][CH2:5][CH3:6])=[O:3])([OH:35])[CH2:31][CH2:32][CH2:33][CH2:34][C:28]=3[N:27]=[C:26]2[C:36]([CH3:39])([CH3:38])[CH3:37])=[CH:22][CH:23]=1

Participants

6

Reactant 4

HCID 8857Ethyl AcetateHCID 25517Ammonium ChlorideHCID 2733832Lithium HexamethyldisilazideHCID 584602383-[(4-chlorophenyl)methyl]-2-(1,1-dimethylethyl)-5,6,7,8-tetrahydrocyclohepta[d]imidazol-4(3H)-one

Product 1

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

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-78 °C

Procedure

Ethyl acetate (0.695 mL) was added dropwise to a stirred solution of LiHMDS, 1M in THF (7.10 ml) cooled to −78° C. under nitrogen atmosphere. The mixture was stirred at −78° C. for 30 minutes. Intermediate 14 was dissolved in THF (3 ml) and added dropwise. The RM was stirred at −78° C. under nitrogen for 2 hours. An excess of sat. NH4Cl aq. sol. added and the resulting suspension warmed up to room temp and extracted with EtOAc (100 ml). The phases were separated and the aqueous layer was again extracted with EtOAc (50 ml), the phases were separated. The organics were combined, dried (hydrophobic frit) and concentrated under vacuum. The residue was purified on silica using a Dichloromethane:Ethyl acetate 0-100% gradient. The desired fractions were combined and concentrated under vacuum to give the title compound (420 mg). LC/MS MH+419, Rt 1.93 min (5 minute run).

Workup

  1. additionadded dropwise
  2. stirringThe RM was stirred at −78° C. under nitrogen for 2 hours
  3. temperaturethe resulting suspension warmed up to room temp
  4. extractionextracted with EtOAc (100 ml)
  5. customThe phases were separated
  6. extractionthe aqueous layer was again extracted with EtOAc (50 ml)
  7. customthe phases were separated
  8. customdried (hydrophobic frit)
  9. concentrationconcentrated under vacuum
  10. customThe residue was purified on silica using a Dichloromethane
  11. concentrationconcentrated under vacuum

Sources & evidence

ORD record
ord-235094cf5cb0411b840c99dd79e3fd38
Source dataset
uspto-grants-2013_03
Patent number
US08399444B2

Reaction notes

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