Triethylamine → 1-(Methoxycarbonyl)-2-(2,4,5-trifluorophenyl)piperidine-4-carboxylic acid

HRID 1963203Notes

Reaction equation

HRID 1963203 reaction equation
[F:1][C:2]1[CH:7]=[C:6]([F:8])[C:5]([F:9])=[CH:4][C:3]=1[CH:10]1[CH2:15][CH:14]([C:16]([O:18]C)=[O:17])[CH2:13][CH2:12][N:11]1[C:20]([O:22][CH3:23])=[O:21].[Br-].[Li+].C(N(CC)CC)C.CC(OC)(C)C>C(#N)C.O>[CH3:23][O:22][C:20]([N:11]1[CH2:12][CH2:13][CH:14]([C:16]([OH:18])=[O:17])[CH2:15][CH:10]1[C:3]1[CH:4]=[C:5]([F:9])[C:6]([F:8])=[CH:7][C:2]=1[F:1])=[O:21]

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 15413tert-Butyl methyl etherHCID 82050Lithium BromideHCID 68502002Dimethyl 2-(2,4,5-trifluorophenyl)piperidine-1,4-dicarboxylate

Product 1

HCID 667323461-(Methoxycarbonyl)-2-(2,4,5-trifluorophenyl)piperidine-4-carboxylic acidYield 84%

Reagents, catalysts & solvents 2

HCID 962WaterSolvent2×HCID 6342AcetonitrileSolvent

Procedure

Dimethyl 2-(2,4,5-trifluorophenyl)piperidine-1,4-dicarboxylate (2.971 g, 8.97 mmol) was dissolved in acetonitrile (30 mL) and water (0.600 mL), then lithium bromide (6.23 g, 71.74 mmol) was added. Triethylamine (4.97 mL, 35.87 mmol) was added and the resulting brown suspension was heated under reflux. Water and MTBE were added. The organic phase was extracted with water (×2). The pooled aqueous layer was acidified to pH 1 with 3.8 M HCl and then extracted with MTBE (×2). The combined organic layer was washed with water and evaporated. Traces of water were azeotropically removed by MeCN. 1-(Methoxycarbonyl)-2-(2,4,5-trifluorophenyl)piperidine-4-carboxylic acid (2.388 g, 84%) was isolated as a yellow oil. MS m/z 318 (M+H)+

Workup

  1. temperaturethe resulting brown suspension was heated
  2. temperatureunder reflux
  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. customTraces of water were azeotropically removed by MeCN

Sources & evidence

ORD record
ord-5325be681e3b4f9e933cb405b37522f0
Source dataset
uspto-grants-2013_04
Patent number
US08415378B2

Reaction notes

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