Hydrochloric Acid → 4-[4-({(tert-butoxycarbonyl)[(1R)-1-(1-naphthyl)ethyl]amino}methyl)-3-phenylpiperidin-1-yl]-3,5-difluorobenzoic acid

HRID 1691765Notes

Reaction equation

HRID 1691765 reaction equation
[C:1]([O:5][C:6]([N:8]([CH2:21][CH:22]1[CH2:27][CH2:26][N:25]([C:28]2[C:37]([F:38])=[CH:36][C:31]([C:32]([O:34]C)=[O:33])=[CH:30][C:29]=2[F:39])[CH2:24][CH:23]1[C:40]1[CH:45]=[CH:44][CH:43]=[CH:42][CH:41]=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:7])([CH3:4])([CH3:3])[CH3:2].C1COCC1.[OH-].[Na+].Cl>CO>[C:1]([O:5][C:6]([N:8]([CH2:21][CH:22]1[CH2:27][CH2:26][N:25]([C:28]2[C:29]([F:39])=[CH:30][C:31]([C:32]([OH:34])=[O:33])=[CH:36][C:37]=2[F:38])[CH2:24][CH:23]1[C:40]1[CH:41]=[CH:42][CH:43]=[CH:44][CH:45]=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:7])([CH3:2])([CH3:3])[CH3:4]

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 8028TetrahydrofuranHCID 14798Sodium HydroxideHCID 66906144methyl 4-[4-({(tert-butoxycarbonyl)[(1R)-1-(1-naphthyl)ethyl]amino}methyl)-3-phenylpiperidin-1-yl]-3,5-difluorobenzoate

Product 1

HCID 669060884-[4-({(tert-butoxycarbonyl)[(1R)-1-(1-naphthyl)ethyl]amino}methyl)-3-phenylpiperidin-1-yl]-3,5-difluorobenzoic acidYield 96.5%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

To a mixture of 247 mg of the crude methyl 4-[4-({(tert-butoxycarbonyl)[(1R)-1-(1-naphthyl)ethyl]amino}methyl)-3-phenylpiperidin-1-yl]-3,5-difluorobenzoate, 4.0 mL of THF, and 2.0 mL of methanol was added dropwise a 1 M aqueous sodium hydroxide solution at room temperature, followed by stirring overnight. The reaction mixture was neutralized by addition of 1 M hydrochloric acid, and then extracted with ethyl acetate, and the organic layer was 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 233 mg of 4-[4-({(tert-butoxycarbonyl)[(1R)-1-(1-naphthyl)ethyl]amino}methyl)-3-phenylpiperidin-1-yl]-3,5-difluorobenzoic acid as a white solid. FAB+: 601

Workup

  1. extractionextracted with ethyl acetate
  2. dry with materialthe organic layer was dried over anhydrous sodium sulfate
  3. filtrationAfter filtration
  4. concentrationthe filtrate was concentrated under reduced pressure
  5. customthe residue was purified by silica gel column chromatography (methanol-chloroform)

Sources & evidence

ORD record
ord-22f9440104314ccc9d330697135a9d6c
Source dataset
uspto-grants-2012_04
Patent number
US08153658B2

Reaction notes

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