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

HRID 1963269Notes

Reaction equation

HRID 1963269 reaction equation
[F:1][C:2]1[CH:22]=[CH:21][C:5]([CH2:6][CH:7]2[CH2:12][CH:11]([C:13]([O:15]C)=[O:14])[CH2:10][CH2:9][N:8]2[C:17]([O:19][CH3:20])=[O:18])=[CH:4][CH:3]=1.[Br-].[Li+].C(N(CC)CC)C.CC(OC)(C)C>C(#N)C.O>[F:1][C:2]1[CH:3]=[CH:4][C:5]([CH2:6][CH:7]2[CH2:12][CH:11]([C:13]([OH:15])=[O:14])[CH2:10][CH2:9][N:8]2[C:17]([O:19][CH3:20])=[O:18])=[CH:21][CH:22]=1

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 15413tert-Butyl methyl etherHCID 82050Lithium BromideHCID 66735290Dimethyl 2-(4-fluorobenzyl)piperidine-1,4-dicarboxylate

Product 1

HCID 667316402-(4-Fluorobenzyl)-1-(methoxycarbonyl)piperidine-4-carboxylic acidYield 80.1%

Reagents, catalysts & solvents 2

HCID 962WaterSolvent2×HCID 6342AcetonitrileSolvent

Procedure

Dimethyl 2-(4-fluorobenzyl)piperidine-1,4-dicarboxylate (5.797 g, 18.74 mmol) was dissolved in acetonitrile (60 mL) and water (1.2 mL), then lithium bromide (13.02 g, 149.92 mmol) was added. Triethylamine (10.39 mL, 74.96 mmol) was added and the resulting yellow suspension was heated at reflux for 1.5 h. water (60 mL) and MTBE (120 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 and evaporated. Traces of water were azeotropically removed by MeCN. 2-(4-Fluorobenzyl)-1-(methoxycarbonyl)piperidine-4-carboxylic acid (4.43 g, 80%) was isolated as a beige solid. MS m/z 296 (M+H)+

Workup

  1. temperaturethe resulting yellow suspension was heated
  2. additionwere added
  3. extractionThe organic phase was extracted with water (×2)
  4. extractionextracted with MTBE (×2)
  5. washThe combined organic layer was washed with water
  6. customevaporated
  7. customTraces of water were azeotropically removed by MeCN

Sources & evidence

ORD record
ord-8e5e82ee04b34bb98348e875bf29e895
Source dataset
uspto-grants-2013_04
Patent number
US08415378B2

Reaction notes

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