HCID 178516319, compound → HCID 178516313, compound

HRID 1788096Notes

Reaction equation

HRID 1788096 reaction equation
Cl[C:2]1[C:13]2[NH:12][N:11]=[N:10][C:9]=2[C:8]2[CH2:7][C:6]34[CH2:24][CH: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>CN(C=O)C.ClCCl.[OH-].[OH-].[Pd+2].[Pd]>[F:21][C:19]([F:20])([F:22])[C:18]1[C:17](=[O:23])[CH:16]2[CH2:24][C:6]3([CH2:7][C:8]4[C:9]5[N:10]=[N:11][NH:12][C:13]=5[CH:2]=[CH:3][C:4]=4[C:5]=13)[CH2:14][CH2:15]2

Participants

6

Reactant 1

HCID 178516319HCID 178516319, compound

Product 1

HCID 178516313HCID 178516313, compound

Reagents, catalysts & solvents 4

HCID 23938PalladiumCatalyst2×HCID 9942167Palladium hydroxideCatalyst2×HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Procedure

To a solution of 4-chloro-6-(trifluoromethyl)-3,9,10,11-tetrahydro-8,10a-methanocyclohepta-[1,2]indeno[4,5-d][1,2,3]triazol-7(8H)-one (2.3 g, crude product from the preceding step, ˜6.1 mmol) in DMF (230 mL) were added 20% Pd(OH)2 on carbon (1 g) and 5% palladium on calcium carbonate (1 g) and the mixture was hydrogenated at atmospheric pressure. After 29 hours, additional 20% Pd(OH)2 on carbon (175 mg) and 5% palladium on calcium carbonate (175 mg) were added. After 24 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 thoroughly extracted with EtOAc and the combined organic layers were washed with 1N hydrochloric acid, water and brine. After drying over MgSO4, the solvent was removed under reduced pressure to give an oily solid which was dissolved in dichloromethane and evaporated to give a solid. Chromatography on silica gel (elution with 1:1 EtOAc/hexanes+0.1% HOAc followed by 99:99:2 EtOAc/hexanes/methanol+0.1% HOAc) gave 6-(trifluoromethyl)-3,9,10,11-tetrahydro-8,10a-methanocyclohepta-[1,2]indeno[4,5-d][1,2,3]triazol-7(8H)-one as a pale yellow solid.

Workup

  1. waitAfter 24 hours more
  2. filtrationthe mixture was filtered through a pad of Celite®
  3. washwashing thoroughly with EtOAc
  4. customThe filtrate was partitioned between EtOAc and water which
  5. extractionThe aqueous layer was thoroughly extracted with EtOAc
  6. washthe combined organic layers were washed with 1N hydrochloric acid, water and brine
  7. dry with materialAfter drying over MgSO4
  8. customthe solvent was removed under reduced pressure
  9. customto give an oily solid which
  10. customevaporated
  11. customto give a solid

Sources & evidence

ORD record
ord-bba0d7e5822746829124c9cba0e9bdee
Source dataset
uspto-grants-2009_03
Patent number
US07511152B2

Reaction notes

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