1,4-Dioxane hydrochloride → 3,5-difluoro-4-[4-(2-fluorophenyl)-3-({[(1R)-1-(1-naphthyl)ethyl]amino}methyl)piperidin-1-yl]benzoic acid

HRID 1691761Notes

Reaction equation

HRID 1691761 reaction equation
C(OC([N:8]([CH2:21][CH:22]1[CH:27]([C:28]2[CH:33]=[CH:32][CH:31]=[CH:30][C:29]=2[F:34])[CH2:26][CH2:25][N:24]([C:35]2[C:43]([F:44])=[CH:42][C:38]([C:39]([OH:41])=[O:40])=[CH:37][C:36]=2[F:45])[CH2:23]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.Cl.O1CCOCC1>>[F:44][C:43]1[CH:42]=[C:38]([CH:37]=[C:36]([F:45])[C:35]=1[N:24]1[CH2:25][CH2:26][CH:27]([C:28]2[CH:33]=[CH:32][CH:31]=[CH:30][C:29]=2[F:34])[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])[CH2:23]1)[C:39]([OH:41])=[O:40]

Participants

3

Reactant 2

HCID 204431481,4-Dioxane hydrochlorideHCID 669064714-[3-({(tert-butoxycarbonyl)[(1R)-1-(1-naphthyl)ethyl]amino}methyl)-4-(2-fluorophenyl)piperidin-1-yl]-3,5-difluorobenzoic acid

Product 1

HCID 591785783,5-difluoro-4-[4-(2-fluorophenyl)-3-({[(1R)-1-(1-naphthyl)ethyl]amino}methyl)piperidin-1-yl]benzoic acidYield 98.1%

Procedure

To 135 mg of 4-[3-({(tert-butoxycarbonyl)[(1R)-1-(1-naphthyl)ethyl]amino}methyl)-4-(2-fluorophenyl)piperidin-1-yl]-3,5-difluorobenzoic acid was added 3.0 mL of a 4 M hydrogen chloride/1,4-dioxane solution, followed by stirring at room temperature overnight. The reaction mixture was concentrated under reduced pressure, and to the obtained residue were added chloroform and a saturated aqueous sodium hydrogen carbonate solution, followed by stirring, and the organic layer was then separated, and dried over anhydrous sodium sulfate. After filtration, the filtrate was concentrated under reduced pressure, and the residue was purified by silica gel column chromatography (methanol-chloroform) to obtain 111 mg of 3,5-difluoro-4-[4-(2-fluorophenyl)-3-({[(1R)-1-(1-naphthyl)ethyl]amino}methyl)piperidin-1-yl]benzoic acid as a colorless amorphous substance. The obtained amorphous substance was dissolved in chloroform, and hexane was added thereto to precipitate a white solid, which was collected by filtration to obtain 93 mg of 3,5-difluoro-4-[4-(2-fluorophenyl)-3-({[(1R)-1-(1-naphthyl)ethyl]amino}methyl)piperidin-1-yl]benzoic acid as a white solid.

Workup

  1. concentrationThe reaction mixture was concentrated under reduced pressure
  2. additionto the obtained residue were added chloroform
  3. stirringby stirring
  4. customthe organic layer was then separated
  5. dry with materialdried over anhydrous sodium sulfate
  6. filtrationAfter filtration
  7. concentrationthe filtrate was concentrated under reduced pressure
  8. customthe residue was purified by silica gel column chromatography (methanol-chloroform)

Sources & evidence

ORD record
ord-be6f223463da45b28866bff63236c65e
Source dataset
uspto-grants-2012_04
Patent number
US08153658B2

Reaction notes

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