HCID 11547019, compound → HCID 11655477, compound

HRID 908986Notes

Reaction equation

HRID 908986 reaction equation
Cl.[CH3:2][N:3]([CH3:32])[C:4]1([C:25]2[CH:30]=[CH:29][CH:28]=[C:27]([F:31])[CH:26]=2)[CH2:9][CH2:8][C:7](=[CH:10][C:11]([NH:13][CH2:14][CH2:15][C:16]2[C:24]3[C:19](=[CH:20][CH:21]=[CH:22][CH:23]=3)[NH:18][CH:17]=2)=[O:12])[CH2:6][CH2:5]1>[Pd].CO>[CH3:32][N:3]([CH3:2])[C:4]1([C:25]2[CH:30]=[CH:29][CH:28]=[C:27]([F:31])[CH:26]=2)[CH2:9][CH2:8][CH:7]([CH2:10][C:11]([NH:13][CH2:14][CH2:15][C:16]2[C:24]3[C:19](=[CH:20][CH:21]=[CH:22][CH:23]=3)[NH:18][CH:17]=2)=[O:12])[CH2:6][CH2:5]1

Participants

4

Reactant 1

HCID 11547019HCID 11547019, compound2×

Product 1

HCID 11655477HCID 11655477, compoundYield 13%

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 887MethanolSolvent

Procedure

Palladium-on-charcoal (5%, 120 mg) was added to a solution of 2-[4-dimethylamino-4-(3-fluorophenyl)-cyclohexylidene]-N-[2-(1H-indol-3-yl)-ethyl]-acetamide (base of Example 25; 660 mg; 1.55 mmol) in abs. methanol (100 ml). The reaction mixture was hydrogenated at 40° C. under a pressure of 3 bar for 20 h. The catalyst was separated off over Celite and the filtrate was concentrated. After separation of the residue by chromatography on silica gel (45 g) with EA/methanol (5:1) and methanol, the less polar diastereoisomer of 2-[4-dimethylamino-4-(3-fluorophenyl)cyclohexyl]-N-[2-(1H-indol-3-yl)ethyl]acetamide was isolated in a yield of 13% (86 mg) and the more polar diastereoisomer of 2-[4-dimethylamino-4-(3-fluorophenyl)cyclohexyl]-N-[2-(1H-indol-3-yl)ethyl]acetamide was isolated in a yield of 59% (391 mg). Both amides were colourless oils and diastereomerically pure.

Workup

  1. customThe catalyst was separated off over Celite
  2. concentrationthe filtrate was concentrated
  3. customAfter separation of the residue by chromatography on silica gel (45 g) with EA/methanol (5:1) and methanol

Sources & evidence

ORD record
ord-92b6258468c7461685b8f9a91980630b
Source dataset
uspto-grants-2011_09
Patent number
US08017630B2

Reaction notes

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