Benzene → HCID 67110521, compound

HRID 2076380Notes

Reaction equation

HRID 2076380 reaction equation
Cl[C:2]1[C:13]2[NH:12][CH:11]=[N:10][C:9]=2[C:8]2[CH2:7][C@:6]34[CH2:24][C@H:16]([C:17](=[O:23])[C:18]([C:19]([F:22])([F:21])[F:20])=[C:5]3[C:4]=2[CH:3]=1)[CH2:15][CH2:14]4.C1C=CC=CC=1.CO>CN(C=O)C.[OH-].[OH-].[Pd+2].[Pd]>[F:21][C:19]([F:20])([F:22])[C:18]1[C:17](=[O:23])[C@H:16]2[CH2:24][C@:6]3([CH2:7][C:8]4[C:9]5[N:10]=[CH:11][NH:12][C:13]=5[CH:2]=[CH:3][C:4]=4[C:5]=13)[CH2:14][CH2:15]2

Participants

7

Reactant 3

HCID 241BenzeneHCID 887MethanolHCID 178516318HCID 178516318, compound

Product 1

HCID 67110521HCID 67110521, compound

Reagents, catalysts & solvents 3

HCID 23938PalladiumCatalyst3×HCID 9942167Palladium hydroxideCatalyst3×HCID 6228DimethylformamideSolvent

Procedure

To a solution of (8R,10aS)-4-chloro-6-(trifluoromethyl)-3,9,10,11-tetrahydro-8,10a-methanocyclohepta[1,2]indeno[4,5-d]imidazol-7(8H)-one (58 mg, 0.16 mmol) in DMF (5.8 mL) were added 20% Pd(OH)2 on carbon (27 mg) and 5% palladium on calcium carbonate (29 mg) and the mixture was hydrogenated at atmospheric pressure. After 16 hours, additional 20% Pd(OH)2 on carbon (12 mg) and 5% palladium on calcium carbonate (12 mg) were added. After another 3.5 hours, additional 20% Pd(OH)2 on carbon (5 mg) and 5% palladium on calcium carbonate (5 mg) were added. After 66 hours more, the mixture was filtered through a pad of Celite®, washing thoroughly with EtOAc. The filtrate was partitioned between EtOAc and water which had been acidified with a small amount of 1N hydrochloric acid. The aqueous layer was neutralized with 5% aqueous sodium bicarbonate and was then thoroughly extracted with EtOAc. After drying over MgSO4, the solvent was removed under reduced pressure to give a gum. Chromatography on silica gel (elution with 5% methanol in dichloromethane) gave a yellow oil which was lyophilized from benzene containing a small amount of methanol to provide (8R,10aS)-6-(trifluoromethyl)-3,9,10,11-tetrahydro-8,10a-methanocyclohepta[1,2]indeno[4,5-d]imidazol-7(8H)-one as a yellow solid.

Workup

  1. waitAfter another 3.5 hours
  2. waitAfter 66 hours more
  3. filtrationthe mixture was filtered through a pad of Celite®
  4. washwashing thoroughly with EtOAc
  5. customThe filtrate was partitioned between EtOAc and water which
  6. extractionwas then thoroughly extracted with EtOAc
  7. dry with materialAfter drying over MgSO4
  8. customthe solvent was removed under reduced pressure
  9. customto give a gum
  10. customChromatography on silica gel (elution with 5% methanol in dichloromethane) gave a yellow oil which

Sources & evidence

ORD record
ord-e0d67ea347b94dad985c4b59b6ce754a
Source dataset
uspto-grants-2011_04
Patent number
US07923568B2

Reaction notes

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