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

HRID 1963324Notes

Reaction equation

HRID 1963324 reaction equation
[Br-].[Li+].C(N(CC)CC)C.[F:10][C:11]1[CH:31]=[C:30]([F:32])[CH:29]=[CH:28][C:12]=1[CH2:13][CH:14]1[CH2:19][CH:18]([C:20]([O:22]C)=[O:21])[CH2:17][CH2:16][N:15]1[C:24]([O:26][CH3:27])=[O:25].CC(OC)(C)C>C(#N)C.O>[F:10][C:11]1[CH:31]=[C:30]([F:32])[CH:29]=[CH:28][C:12]=1[CH2:13][CH:14]1[CH2:19][CH:18]([C:20]([OH:22])=[O:21])[CH2:17][CH2:16][N:15]1[C:24]([O:26][CH3:27])=[O:25]

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 15413tert-Butyl methyl etherHCID 82050Lithium BromideHCID 66734674Dimethyl 2-(2,4-difluorobenzyl)piperidine-1,4-dicarboxylate

Product 1

HCID 667324712-(2,4-Difluorobenzyl)-1-(methoxycarbonyl)piperidine-4-carboxylic acidYield 92%

Reagents, catalysts & solvents 2

HCID 962WaterSolvent2×HCID 6342AcetonitrileSolvent2×

Procedure

To a suspension of lithium bromide (18.06 g, 207.99 mmol) in acetonitrile (80 mL) and water (1.6 mL) was added triethylamine (14.42 mL, 104.00 mmol) followed by dimethyl 2-(2,4-difluorobenzyl)piperidine-1,4-dicarboxylate (8.51 g, 26.00 mmol) in acetonitrile (40 mL). The resulting mixture was heated under reflux for 2 h 30 min, then cooled to room temperature and water and MTBE were added. The organic phase was extracted with water twice. The pooled aqueous layers were adjusted to pH 1 with 3.8 M HCl and then extracted with DCM (3×). The combined organic layers were dried over MgSO4 and evaporated to yield 2-(2,4-difluorobenzyl)-1-(methoxycarbonyl)piperidine-4-carboxylic acid (7.48 g, 92%) as an orange solid. MS m/z 314 (M+H)+

Workup

  1. temperatureThe resulting mixture was heated
  2. temperatureunder reflux for 2 h 30 min
  3. extractionThe organic phase was extracted with water twice
  4. extractionextracted with DCM (3×)
  5. dry with materialThe combined organic layers were dried over MgSO4
  6. customevaporated

Sources & evidence

ORD record
ord-91e53096c4f148919f3b3842311204a1
Source dataset
uspto-grants-2013_04
Patent number
US08415378B2

Reaction notes

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