Triethylamine → 2-(3,4-Difluorobenzyl)-1-(methoxycarbonyl)piperidine-4-carboxylic acid

HRID 1963308Notes

Reaction equation

HRID 1963308 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([CH:20]=[CH:21][C:22]=1[F:23])[CH2:5][CH:6]1[CH2:11][CH:10]([C:12]([O:14]C)=[O:13])[CH2:9][CH2:8][N:7]1[C:16]([O:18][CH3:19])=[O:17].[Br-].[Li+].C(N(CC)CC)C.CC(OC)(C)C>C(#N)C.O>[F:1][C:2]1[CH:3]=[C:4]([CH:20]=[CH:21][C:22]=1[F:23])[CH2:5][CH:6]1[CH2:11][CH:10]([C:12]([OH:14])=[O:13])[CH2:9][CH2:8][N:7]1[C:16]([O:18][CH3:19])=[O:17]

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 15413tert-Butyl methyl etherHCID 82050Lithium BromideHCID 66734915Dimethyl 2-(3,4-difluorobenzyl)piperidine-1,4-dicarboxylate

Product 1

HCID 667318192-(3,4-Difluorobenzyl)-1-(methoxycarbonyl)piperidine-4-carboxylic acidYield 99%

Reagents, catalysts & solvents 2

HCID 962WaterSolvent2×HCID 6342AcetonitrileSolvent

Procedure

Dimethyl 2-(3,4-difluorobenzyl)piperidine-1,4-dicarboxylate (7.010 g, 21.42 mmol) was dissolved in acetonitrile (75 mL) and water (1.5 mL). Lithium bromide (14.88 g, 171.33 mmol) and triethylamine (11.87 mL, 85.66 mmol) were added and the resulting yellow suspension was heated at reflux for 3 h. Water (100 mL) and MTBE (300 mL) were added. The organic phase was extracted with water (×2). The pooled aqueous layer was acidified to pH 1 with 3.8 M HCl and then extracted with MTBE (×2). The combined organic layer was washed with water, dried over Na2SO4, filtered and evaporated to yield 2-(3,4-difluorobenzyl)-1-(methoxycarbonyl)piperidine-4-carboxylic acid (6.62 g, 99%) as a yellow solid. MS m/z 314 (M+H)+

Workup

  1. temperaturethe resulting yellow suspension was heated
  2. temperatureat reflux for 3 h
  3. extractionThe organic phase was extracted with water (×2)
  4. extractionextracted with MTBE (×2)
  5. washThe combined organic layer was washed with water
  6. dry with materialdried over Na2SO4
  7. filtrationfiltered
  8. customevaporated

Sources & evidence

ORD record
ord-1bfb74ea3879453b8687dfec779a5a5a
Source dataset
uspto-grants-2013_04
Patent number
US08415378B2

Reaction notes

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