Triethylamine → 2-(3-tert-Butylphenyl)-1-(methoxycarbonyl)piperidine-4-carboxylic acid

HRID 1963152Notes

Reaction equation

HRID 1963152 reaction equation
[C:1]([C:5]1[CH:6]=[C:7]([CH:11]2[CH2:16][CH:15]([C:17]([O:19]C)=[O:18])[CH2:14][CH2:13][N:12]2[C:21]([O:23][CH3:24])=[O:22])[CH:8]=[CH:9][CH:10]=1)([CH3:4])([CH3:3])[CH3:2].[Br-].[Li+].C(N(CC)CC)C.CC(OC)(C)C>C(#N)C.O>[C:1]([C:5]1[CH:6]=[C:7]([CH:11]2[CH2:16][CH:15]([C:17]([OH:19])=[O:18])[CH2:14][CH2:13][N:12]2[C:21]([O:23][CH3:24])=[O:22])[CH:8]=[CH:9][CH:10]=1)([CH3:4])([CH3:2])[CH3:3]

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 15413tert-Butyl methyl etherHCID 82050Lithium BromideHCID 66734775Dimethyl 2-(3-tert-butylphenyl)piperidine-1,4-dicarboxylate

Product 1

HCID 667322282-(3-tert-Butylphenyl)-1-(methoxycarbonyl)piperidine-4-carboxylic acidYield 90%

Reagents, catalysts & solvents 2

HCID 962WaterSolvent2×HCID 6342AcetonitrileSolvent

Procedure

Dimethyl 2-(3-tert-butylphenyl)piperidine-1,4-dicarboxylate (3.17 g, 9.51 mmol) was dissolved in acetonitrile (60 mL) and water (1.200 mL), then lithium bromide (6.61 g, 76.06 mmol) was added in one portion. Triethylamine (5.27 mL, 38.03 mmol) was added and the resulting brown suspension was heated under reflux for 1.5 h. Water (120 mL) and MTBE (120 mL) were added. The organic phase was extracted with water (2×25 mL). The pooled aqueous layer was acidified to pH 1 with 0.5 M HCl (30 mL) and extracted with MTBE (2×150 mL). The combined organic layer was washed with water (25 mL), dried over Na2SO4 and evaporated. 2-(3-tert-Butylphenyl)-1-(methoxycarbonyl)piperidine-4-carboxylic acid (2.73 g, 90%) was isolated as a foam.

Workup

  1. temperaturethe resulting brown suspension was heated
  2. temperatureunder reflux for 1.5 h
  3. extractionThe organic phase was extracted with water (2×25 mL)
  4. extractionextracted with MTBE (2×150 mL)
  5. washThe combined organic layer was washed with water (25 mL)
  6. dry with materialdried over Na2SO4
  7. customevaporated

Sources & evidence

ORD record
ord-7428f93141a949cc9b9a48ac957ad47b
Source dataset
uspto-grants-2013_04
Patent number
US08415378B2

Reaction notes

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