Triethylamine → 2-(2,6-Difluorobenzyl)-1-(methoxycarbonyl)piperidine-4-carboxylic acid

HRID 1963316Notes

Reaction equation

HRID 1963316 reaction equation
[F:1][C:2]1[CH:22]=[CH:21][CH:20]=[C:19]([F:23])[C:3]=1[CH2:4][CH:5]1[CH2:10][CH:9]([C:11]([O:13]C)=[O:12])[CH2:8][CH2:7][N:6]1[C:15]([O:17][CH3:18])=[O:16].[Br-].[Li+].C(N(CC)CC)C.CC(OC)(C)C>C(#N)C.O>[F:1][C:2]1[CH:22]=[CH:21][CH:20]=[C:19]([F:23])[C:3]=1[CH2:4][CH:5]1[CH2:10][CH:9]([C:11]([OH:13])=[O:12])[CH2:8][CH2:7][N:6]1[C:15]([O:17][CH3:18])=[O:16]

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 15413tert-Butyl methyl etherHCID 82050Lithium BromideHCID 66734964Dimethyl 2-(2,6-difluorobenzyl)piperidine-1,4-dicarboxylate

Product 1

HCID 667316802-(2,6-Difluorobenzyl)-1-(methoxycarbonyl)piperidine-4-carboxylic acidYield 82.5%

Reagents, catalysts & solvents 2

HCID 962WaterSolvent2×HCID 6342AcetonitrileSolvent

Procedure

Dimethyl 2-(2,6-difluorobenzyl)piperidine-1,4-dicarboxylate (5.98 g, 18.27 mmol) was dissolved in acetonitrile (50 mL) and water (1 mL), then lithium bromide (12.69 g, 146.16 mmol) and triethylamine (10.13 mL, 73.08 mmol) were added. The suspension was heated to reflux for 3.5 h, then water (60 mL) and MTBE (180 mL) were added. The organic phase was extracted with water (×2). The combined water phases were acidified to pH 1 with 3.8 M HCl and extracted with MTBE (×2). The combined organic phases were washed with water, dried with MgSO4, filtered through celite and concentrated to give 2-(2,6-difluorobenzyl)-1-(methoxycarbonyl)piperidine-4-carboxylic acid (4.72 g, 82%) as a light yellow solid. MS m/z 314 (M+H)+

Workup

  1. temperatureThe suspension was heated
  2. temperatureto reflux for 3.5 h
  3. extractionThe organic phase was extracted with water (×2)
  4. extractionextracted with MTBE (×2)
  5. washThe combined organic phases were washed with water
  6. dry with materialdried with MgSO4
  7. filtrationfiltered through celite and
  8. concentrationconcentrated

Sources & evidence

ORD record
ord-f1aa74f13a2c4286a482d944903eb5c4
Source dataset
uspto-grants-2013_04
Patent number
US08415378B2

Reaction notes

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