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

HRID 1691691Notes

Reaction equation

HRID 1691691 reaction equation
[C:1]([O:5][C:6]([N:8]([CH2:21][CH:22]1[CH:27]([C:28]2[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=2)[CH2:26][CH2:25][N:24]([C:34]2[C:43]([F:44])=[CH:42][C:37]([C:38]([O:40]C)=[O:39])=[CH:36][C:35]=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: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[CH:27]([C:28]2[CH:29]=[CH:30][CH:31]=[CH:32][CH:33]=2)[CH2:26][CH2:25][N:24]([C:34]2[C:43]([F:44])=[CH:42][C:37]([C:38]([OH:40])=[O:39])=[CH:36][C:35]=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:7])([CH3:2])([CH3:3])[CH3:4]

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 8028TetrahydrofuranHCID 14798Sodium HydroxideHCID 66906171methyl 4-[3-({(tert-butoxycarbonyl)[(1R)-1-(1-naphthyl)ethyl]amino}methyl)-4-phenylpiperidin-1-yl]-3,5-difluorobenzoate

Product 1

HCID 669059254-[3-({(tert-butoxycarbonyl)[(1R)-1-(1-naphthyl)ethyl]amino}methyl)-4-phenylpiperidin-1-yl]-3,5-difluorobenzoic acidYield 96.5%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

To 122 mg of methyl 4-[3-({(tert-butoxycarbonyl)[(1R)-1-(1-naphthyl)ethyl]amino}methyl)-4-phenylpiperidin-1-yl]-3,5-difluorobenzoate were added 2.0 mL of THF, 2.0 mL of methanol, and 1.0 mL of a 1 M aqueous sodium hydroxide solution, followed by stirring at room temperature overnight. It was neutralized by addition of 1.1 mL 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 (chloroform-methanol) to obtain 115 mg of 4-[3-({(tert-butoxycarbonyl)[(1R)-1-(1-naphthyl)ethyl]amino}methyl)-4-phenylpiperidin-1-yl]-3,5-difluorobenzoic acid as a pale yellow oily substance. ESI+: 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 (chloroform-methanol)

Sources & evidence

ORD record
ord-545d8fd6309448429e20b9b2301d0b37
Source dataset
uspto-grants-2012_04
Patent number
US08153658B2

Reaction notes

Loading…