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

HRID 1963277Notes

Reaction equation

HRID 1963277 reaction equation
[F:1][C:2]1[CH:22]=[CH:21][CH:20]=[CH:19][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]=[CH:19][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 66734736Dimethyl 2-(2-fluorobenzyl)piperidine-1,4-dicarboxylate

Product 1

HCID 667323532-(2-Fluorobenzyl)-1-(methoxycarbonyl)piperidine-4-carboxylic acidYield 76.2%

Reagents, catalysts & solvents 2

HCID 962WaterSolvent2×HCID 6342AcetonitrileSolvent

Procedure

Dimethyl 2-(2-fluorobenzyl)piperidine-1,4-dicarboxylate (6.16 g, crude) was dissolved in acetonitrile (45 mL) and water (0.9 mL). Lithium bromide (13.84 g, 159.39 mmol) and triethylamine (11.05 mL, 79.69 mmol) were added and the mixture was heated at reflux overnight. Water (90 mL) and MTBE were added. The organic phase was extracted with water (×2). To the pooled aqueous layer was added MTBE and the solution was acidified to pH 1 with 2 M HCl and then extracted with MTBE (×2). The combined organic layer was dried over Na2SO4 and evaporated to give 2-(2-fluorobenzyl)-1-(methoxycarbonyl)piperidine-4-carboxylic acid (4.48 g, 76%) as a slightly yellow semisolid. MS m/z 296 (M+H)+

Workup

  1. temperaturethe mixture was heated
  2. temperatureat reflux overnight
  3. extractionThe organic phase was extracted with water (×2)
  4. additionTo the pooled aqueous layer was added MTBE
  5. extractionextracted with MTBE (×2)
  6. dry with materialThe combined organic layer was dried over Na2SO4
  7. customevaporated

Sources & evidence

ORD record
ord-d119518a961a450582c74fcce59781d2
Source dataset
uspto-grants-2013_04
Patent number
US08415378B2

Reaction notes

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