1,4-Dioxane hydrochloride → 3,5-difluoro-4-[4-({[(1R)-1-(1-naphthyl)ethyl]amino}methyl)-3-phenylpiperidin-1-yl]benzoic acid hydrochloride

HRID 1691766Notes

Reaction equation

HRID 1691766 reaction equation
C(OC([N:8]([CH2:21][CH:22]1[CH2:27][CH2:26][N:25]([C:28]2[C:36]([F:37])=[CH:35][C:31]([C:32]([OH:34])=[O:33])=[CH:30][C:29]=2[F:38])[CH2:24][CH:23]1[C:39]1[CH:44]=[CH:43][CH:42]=[CH:41][CH:40]=1)[C@@H:9]([C:11]1[C:20]2[C:15](=[CH:16][CH:17]=[CH:18][CH:19]=2)[CH:14]=[CH:13][CH:12]=1)[CH3:10])=O)(C)(C)C.[ClH:45].O1CCOCC1>>[ClH:45].[F:37][C:36]1[CH:35]=[C:31]([CH:30]=[C:29]([F:38])[C:28]=1[N:25]1[CH2:26][CH2:27][CH:22]([CH2:21][NH:8][C@@H:9]([C:11]2[C:20]3[C:15](=[CH:16][CH:17]=[CH:18][CH:19]=3)[CH:14]=[CH:13][CH:12]=2)[CH3:10])[CH:23]([C:39]2[CH:44]=[CH:43][CH:42]=[CH:41][CH:40]=2)[CH2:24]1)[C:32]([OH:34])=[O:33]

Participants

3

Reactant 2

HCID 204431481,4-Dioxane hydrochlorideHCID 669060884-[4-({(tert-butoxycarbonyl)[(1R)-1-(1-naphthyl)ethyl]amino}methyl)-3-phenylpiperidin-1-yl]-3,5-difluorobenzoic acid

Product 1

HCID 669061983,5-difluoro-4-[4-({[(1R)-1-(1-naphthyl)ethyl]amino}methyl)-3-phenylpiperidin-1-yl]benzoic acid hydrochloride

Procedure

To 230 mg of 4-[4-({(tert-butoxycarbonyl)[(1R)-1-(1-naphthyl)ethyl]amino}methyl)-3-phenylpiperidin-1-yl]-3,5-difluorobenzoic acid was added 1.5 mL of a 4 M hydrogen chloride/1,4-dioxane solution at room temperature. After stirring at room temperature for 2 hours, the reaction mixture was concentrated under reduced pressure. The obtained residue was solidified by isopropanol and diisopropyl ether, and then collected by filtration. The obtained solid was purified by silica gel column chromatography (methanol-chloroform), and a 4 M hydrogen chloride/1,4-dioxane solution was then added thereto. The mixture was concentrated under reduced pressure, and the obtained individual product was washed with isopropanol to obtain 140 mg of 3,5-difluoro-4-[4-({[(1R)-1-(1-naphthyl)ethyl]amino}methyl)-3-phenylpiperidin-1-yl]benzoic acid hydrochloride.

Workup

  1. concentrationthe reaction mixture was concentrated under reduced pressure
  2. filtrationcollected by filtration
  3. customThe obtained solid was purified by silica gel column chromatography (methanol-chloroform)
  4. additiona 4 M hydrogen chloride/1,4-dioxane solution was then added
  5. concentrationThe mixture was concentrated under reduced pressure
  6. washthe obtained individual product was washed with isopropanol

Sources & evidence

ORD record
ord-a28ce87c9c9744ada164c5ce5b51f18b
Source dataset
uspto-grants-2012_04
Patent number
US08153658B2

Reaction notes

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