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

HRID 1963273Notes

Reaction equation

HRID 1963273 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([CH:20]=[CH:21][CH:22]=1)[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][CH:22]=1)[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 66734612Dimethyl 2-(3-fluorobenzyl)piperidine-1,4-dicarboxylate

Product 1

HCID 667325072-(3-Fluorobenzyl)-1-(methoxycarbonyl)piperidine-4-carboxylic acidYield 81%

Reagents, catalysts & solvents 2

HCID 962WaterSolvent2×HCID 6342AcetonitrileSolvent

Procedure

Dimethyl 2-(3-fluorobenzyl)piperidine-1,4-dicarboxylate (9.153 g, 29.59 mmol) was dissolved in acetonitrile (100 mL) and water (2 mL), then lithium bromide (20.56 g, 236.72 mmol) was added. Triethylamine (16.41 mL, 118.36 mmol) was added and the resulting brown suspension was heated at reflux for 2 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 through a Celite containing filter and evaporated. 2-(3-Fluorobenzyl)-1-(methoxycarbonyl)piperidine-4-carboxylic acid (7.07 g, 81%) was isolated as a yellow solid. MS m/z 296 (M+H)+

Workup

  1. temperaturethe resulting brown suspension was heated
  2. temperatureat reflux for 2 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 through a Celite
  8. additioncontaining
  9. filtrationfilter
  10. customevaporated

Sources & evidence

ORD record
ord-17934ee07343465689d70a196658a3d5
Source dataset
uspto-grants-2013_04
Patent number
US08415378B2

Reaction notes

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