Hydrochloric Acid → 1-(Methoxycarbonyl)-2-(3-(trifluoromethyl)benzyl)piperidine-4-carboxylic acid

HRID 1963286Notes

Reaction equation

HRID 1963286 reaction equation
[F:1][C:2]([F:25])([F:24])[C:3]1[CH:4]=[C:5]([CH:21]=[CH:22][CH:23]=1)[CH2:6][CH:7]1[CH2:12][CH:11]([C:13]([O:15]C)=[O:14])[CH2:10][CH2:9][N:8]1[C:17]([O:19][CH3:20])=[O:18].[Li+].[Br-].C(N(CC)CC)C.Cl>C(#N)C.O.C(OCC)(=O)C>[CH3:20][O:19][C:17]([N:8]1[CH2:9][CH2:10][CH:11]([C:13]([OH:15])=[O:14])[CH2:12][CH:7]1[CH2:6][C:5]1[CH:21]=[CH:22][CH:23]=[C:3]([C:2]([F:25])([F:24])[F:1])[CH:4]=1)=[O:18]

Participants

8

Reactant 4

HCID 313Hydrochloric AcidHCID 8471TriethylamineHCID 82050Lithium BromideHCID 66734588HCID 66734588, compound

Product 1

HCID 667318321-(Methoxycarbonyl)-2-(3-(trifluoromethyl)benzyl)piperidine-4-carboxylic acidYield 99%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6342AcetonitrileSolventHCID 8857Ethyl AcetateSolvent

Procedure

Dimethyl 2-(3-(trifluoromethyl)benzyl)piperidine-1,4-dicarboxylate (6.1 g, 16.98 mmol) and LiBr (11.79 g, 135.8 mmol) were dissolved in acetonitrile (60 mL) and water (1.2 mL). Triethylamine (9.41 mL, 67.90 mmol) was added and the resulting suspension was heated at reflux for 1 h, then cooled to room temperature and stirred overnight. Dissolved between ethyl acetate and 3 M HCl. The water layer was extracted once with ethyl acetate. The combined organic layers were dried over Na2SO4, filtered through celite and the solvent was evaporated to yield 1-(methoxycarbonyl)-2-(3-(trifluoromethyl)benzyl)piperidine-4-carboxylic acid (5.8 g, 99%).

Workup

  1. temperaturethe resulting suspension was heated
  2. temperatureat reflux for 1 h
  3. extractionThe water layer was extracted once with ethyl acetate
  4. dry with materialThe combined organic layers were dried over Na2SO4
  5. filtrationfiltered through celite
  6. customthe solvent was evaporated

Sources & evidence

ORD record
ord-7729fcf92f704b1ba90b1b7c27e0c861
Source dataset
uspto-grants-2013_04
Patent number
US08415378B2

Reaction notes

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