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

HRID 1963156Notes

Reaction equation

HRID 1963156 reaction equation
[C:1]([C:5]1[CH:10]=[CH:9][C:8]([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:7][CH:6]=1)([CH3:4])([CH3:3])[CH3:2].[Br-].[Li+].C(N(CC)CC)C.O>CC#N>[C:1]([C:5]1[CH:10]=[CH:9][C:8]([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:7][CH:6]=1)([CH3:4])([CH3:2])[CH3:3]

Participants

6

Reactant 4

HCID 962WaterHCID 8471TriethylamineHCID 82050Lithium BromideHCID 66734603Dimethyl 2-(4-tert-butylphenyl)piperidine-1,4-dicarboxylate

Product 1

HCID 667319312-(4-tert-Butylphenyl)-1-(methoxycarbonyl)piperidine-4-carboxylic acidYield 91%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

To a solution of dimethyl 2-(4-tert-butylphenyl)piperidine-1,4-dicarboxylate (10.937 g, 32.80 mmol) in MeCN (100 mL) was added lithium bromide (6.58 mL, 262.42 mmol), triethylamine (18.19 mL, 131.21 mmol) and water (2 mL). The resulting mixture was heated under reflux for 3 h, then cooled to room temperature. The solvents were evaporated and the residue dissolved in water. The aqueous layer was washed with MTBE, then acidified by the addition of 3.8 N HCl. The aqueous layer was extracted three times with DCM. The combined organic layers were dried over MgSO4 and evaporated. 2-(4-tert-Butylphenyl)-1-(methoxycarbonyl)piperidine-4-carboxylic acid (9.5 g, 91%) was isolated as a light brown foam. MS m/z 320 (M+H)+

Workup

  1. temperatureThe resulting mixture was heated
  2. temperatureunder reflux for 3 h
  3. customThe solvents were evaporated
  4. dissolutionthe residue dissolved in water
  5. washThe aqueous layer was washed with MTBE
  6. additionacidified by the addition of 3.8 N HCl
  7. extractionThe aqueous layer was extracted three times with DCM
  8. dry with materialThe combined organic layers were dried over MgSO4
  9. customevaporated

Sources & evidence

ORD record
ord-4147909142804bbfb7df9adbf504a436
Source dataset
uspto-grants-2013_04
Patent number
US08415378B2

Reaction notes

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