Hydrochloric Acid → (2S, 3S)-3-(5-(1,1-Difluoroethyl)-2-(trifluoromethoxy)benzyl)amino-2-phenylpiperidine

HRID 1634330Notes

Reaction equation

HRID 1634330 reaction equation
C(OC([N:8]1[CH2:13][CH2:12][CH2:11][C@H:10]([NH:14][CH2:15][C:16]2[CH:21]=[C:20]([C:22]([F:25])([F:24])[CH3:23])[CH:19]=[CH:18][C:17]=2[O:26][C:27]([F:30])([F:29])[F:28])[C@@H:9]1[C:31]1[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=1)=O)(C)(C)C.Cl.[OH-].[Na+]>C(OCC)(=O)C>[F:25][C:22]([C:20]1[CH:19]=[CH:18][C:17]([O:26][C:27]([F:28])([F:29])[F:30])=[C:16]([CH:21]=1)[CH2:15][NH:14][C@H:10]1[CH2:11][CH2:12][CH2:13][NH:8][C@H:9]1[C:31]1[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=1)([F:24])[CH3:23]

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 70001814(2S,3S)-1-tert-Butoxycarbonyl-3-(5-(1,1-difluoroethyl)-2-(trifluoromethoxy)benzyl)amino-2-phenylpiperidine

Product 1

HCID 57090611(2S, 3S)-3-(5-(1,1-Difluoroethyl)-2-(trifluoromethoxy)benzyl)amino-2-phenylpiperidineYield 70%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Procedure

To a stirred solution of Compound 26 (660 mg, 1.25 mmol) in ethyl acetate (6 ml) was added c. HCl aq. (2 ml) with ice-cooling. The reaction mixture was stirred at room temperature for 50 min. The mixture was basified to pH10-11 with 10% NaOH aq. with ice-cooling. The organic layer was separated and the aqueous layer was extracted with AcOEt. The combined solution was washed with brine, dried (MgSO4), and concentrated in vacuo to give crude product as a pale yellow oil. The crude product was purified by column chromatography on silica gel with dichloromethane-methanol (20:1) to give Compound 27 (360 mg, 70%) as a yellow oil.

Workup

  1. temperaturecooling
  2. customThe organic layer was separated
  3. extractionthe aqueous layer was extracted with AcOEt
  4. washThe combined solution was washed with brine
  5. dry with materialdried (MgSO4)
  6. concentrationconcentrated in vacuo
  7. customto give crude product as a pale yellow oil
  8. customThe crude product was purified by column chromatography on silica gel with dichloromethane-methanol (20:1)

Sources & evidence

ORD record
ord-b0abc6a4662f414f952e2f440e699e29
Source dataset
uspto-grants-2003_01
Patent number
US06506775B1

Reaction notes

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