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

HRID 1963218Notes

Reaction equation

HRID 1963218 reaction equation
[CH3:1][C:2]1[CH:7]=[C:6]([C:8]([F:11])([F:10])[F:9])[CH:5]=[CH:4][C:3]=1[CH:12]1[CH2:17][CH:16]([C:18]([O:20]C)=[O:19])[CH2:15][CH2:14][N:13]1[C:22]([O:24][CH3:25])=[O:23].[Br-].[Li+].C(N(CC)CC)C>C(#N)C.O>[CH3:25][O:24][C:22]([N:13]1[CH2:14][CH2:15][CH:16]([C:18]([OH:20])=[O:19])[CH2:17][CH:12]1[C:3]1[CH:4]=[CH:5][C:6]([C:8]([F:11])([F:9])[F:10])=[CH:7][C:2]=1[CH3:1])=[O:23]

Participants

6

Reactant 3

HCID 8471TriethylamineHCID 82050Lithium BromideHCID 66734452Dimethyl 2-(2-methyl-4-(trifluoromethyl)phenyl)piperidine-1,4-dicarboxylate

Product 1

HCID 667318401-(Methoxycarbonyl)-2-(2-methyl-4-(trifluoromethyl)phenyl)piperidine-4-carboxylic acidYield 91.1%

Reagents, catalysts & solvents 2

HCID 962WaterSolvent2×HCID 6342AcetonitrileSolvent

Procedure

Dimethyl 2-(2-methyl-4-(trifluoromethyl)phenyl)piperidine-1,4-dicarboxylate (8.9 g, 24.77 mmol) was dissolved in acetonitrile (80 mL). Water (1.6 mL), lithium bromide (17.21 g, 198.14 mmol), and triethylamine (13.73 mL, 99.07 mmol) were added. The mixture was heated at reflux for 2.5 h. After cooling it was diluted with water and extracted with EtOAc twice and the combined organic layer washed with water. The combined aqueous layer was acidified with 2 M HCl and extracted three times with EtOAc. The combined organic layer was dried over Na2SO4, filtered and evaporated to give crude 1-(methoxycarbonyl)-2-(2-methyl-4-(trifluoromethyl)phenyl)piperidine-4-carboxylic acid (7.79 g, 91%). MS m/z 344 (M−H)−

Workup

  1. temperatureThe mixture was heated
  2. temperatureat reflux for 2.5 h
  3. temperatureAfter cooling it
  4. extractionextracted with EtOAc twice
  5. washthe combined organic layer washed with water
  6. extractionextracted three times with EtOAc
  7. dry with materialThe combined organic layer was dried over Na2SO4
  8. filtrationfiltered
  9. customevaporated

Sources & evidence

ORD record
ord-161bb363ef694ed6abacf417c48a0aa1
Source dataset
uspto-grants-2013_04
Patent number
US08415378B2

Reaction notes

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