Triethylamine → 1-(Methoxycarbonyl)-2-(4-(trifluoromethyl)phenyl)piperidine-4-carboxylic acid

HRID 1963148Notes

Reaction equation

HRID 1963148 reaction equation
[F:1][C:2]([F:24])([F:23])[C:3]1[CH:8]=[CH:7][C:6]([CH:9]2[CH2:14][CH:13]([C:15]([O:17]C)=[O:16])[CH2:12][CH2:11][N:10]2[C:19]([O:21][CH3:22])=[O:20])=[CH:5][CH:4]=1.[Br-].[Li+].C(N(CC)CC)C.CC(OC)(C)C>C(#N)C.O>[CH3:22][O:21][C:19]([N:10]1[CH2:11][CH2:12][CH:13]([C:15]([OH:17])=[O:16])[CH2:14][CH:9]1[C:6]1[CH:5]=[CH:4][C:3]([C:2]([F:24])([F:1])[F:23])=[CH:8][CH:7]=1)=[O:20]

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 15413tert-Butyl methyl etherHCID 82050Lithium BromideHCID 66734728Dimethyl 2-(4-(trifluoromethyl)phenyl)piperidine-1,4-dicarboxylate

Product 1

HCID 667324851-(Methoxycarbonyl)-2-(4-(trifluoromethyl)phenyl)piperidine-4-carboxylic acidYield 99.3%

Reagents, catalysts & solvents 2

HCID 962WaterSolvent2×HCID 6342AcetonitrileSolvent

Procedure

Dimethyl 2-(4-(trifluoromethyl)phenyl)piperidine-1,4-dicarboxylate (5.996 g, 17.36 mmol) was dissolved in acetonitrile (60 mL) and water (1.200 mL), then lithium bromide (12.06 g, 138.91 mmol) was added. Triethylamine (9.63 mL, 69.46 mmol) was added and the resulting brown suspension was heated under reflux for 1 h. Water and MTBE were added. The organic phase was extracted with water (×2). The combined aqueous layer was acidified to pH 1 with 3.8 M aq HCl and then extracted with MTBE (×2). The combined organic layer was washed with water and evaporated. Trace of water was azeotropically removed by MeCN. 1-(Methoxycarbonyl)-2-(4-(trifluoromethyl)phenyl)piperidine-4-carboxylic acid (5.71 g, 99%) was isolated as a brown oil. MS m/z 332 (M+H)+

Workup

  1. temperaturethe resulting brown suspension was heated
  2. temperatureunder reflux for 1 h
  3. extractionThe organic phase was extracted with water (×2)
  4. extractionextracted with MTBE (×2)
  5. washThe combined organic layer was washed with water
  6. customevaporated
  7. customTrace of water was azeotropically removed by MeCN

Sources & evidence

ORD record
ord-a0e0f06e9f8846a5a38dd5f69eb86528
Source dataset
uspto-grants-2013_04
Patent number
US08415378B2

Reaction notes

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