Triethylamine → 2-(4-Fluorophenethyl)-1-(methoxycarbonyl)piperidine-4-carboxylic acid

HRID 1963261Notes

Reaction equation

HRID 1963261 reaction equation
[F:1][C:2]1[CH:23]=[CH:22][C:5]([CH2:6][CH2:7][CH:8]2[CH2:13][CH:12]([C:14]([O:16]C)=[O:15])[CH2:11][CH2:10][N:9]2[C:18]([O:20][CH3:21])=[O:19])=[CH:4][CH:3]=1.[Br-].[Li+].C(N(CC)CC)C>C(#N)C.O.CC(OC)(C)C>[F:1][C:2]1[CH:3]=[CH:4][C:5]([CH2:6][CH2:7][CH:8]2[CH2:13][CH:12]([C:14]([OH:16])=[O:15])[CH2:11][CH2:10][N:9]2[C:18]([O:20][CH3:21])=[O:19])=[CH:22][CH:23]=1

Participants

7

Reactant 3

HCID 8471TriethylamineHCID 82050Lithium BromideHCID 86646603Dimethyl 2-(4-fluorophenethyl)piperidine-1,4-dicarboxylate

Product 1

HCID 667324832-(4-Fluorophenethyl)-1-(methoxycarbonyl)piperidine-4-carboxylic acidYield 143.7%

Reagents, catalysts & solvents 3

HCID 962WaterSolvent2×HCID 6342AcetonitrileSolventHCID 15413tert-Butyl methyl etherSolvent

Procedure

Dimethyl 2-(4-fluorophenethyl)piperidine-1,4-dicarboxylate (3.18 g, 9.83 mmol) was dissolved in acetonitrile (35 mL) and water (0.7 mL) and lithium bromide (6.83 g, 78.67 mmol) was added. Triethylamine (5.45 mL, 39.34 mmol) was added and the resulting suspension was heated under reflux for 5 h. MTBE and water were added, the phases separated and the organic layer was extracted with water. The combined aqueous layers were acidified to pH 1 with 3.8 M HCl and extracted with MTBE. The combined organic layers were washed with water, dried with Na2SO4 and evaporated. Crude 2-(4-fluorophenethyl)-1-(methoxycarbonyl)piperidine-4-carboxylic acid (4.37 g) was isolated. MS m/z 310 (M+H)+

Workup

  1. temperaturethe resulting suspension was heated
  2. temperatureunder reflux for 5 h
  3. customthe phases separated
  4. extractionthe organic layer was extracted with water
  5. extractionextracted with MTBE
  6. washThe combined organic layers were washed with water
  7. dry with materialdried with Na2SO4
  8. customevaporated

Sources & evidence

ORD record
ord-3cad11dcf3e94f9a954b52bd743903db
Source dataset
uspto-grants-2013_04
Patent number
US08415378B2

Reaction notes

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