Water → Piperidine-1,2,6-tricarboxylic acid 1-benzyl ester

HRID 987078Notes

Reaction equation

HRID 987078 reaction equation
[N:1]1[C:6]([C:7]([OH:9])=[O:8])=[CH:5][CH:4]=[CH:3][C:2]=1[C:10]([OH:12])=[O:11].O.Cl[C:15]([O:17][CH2:18][C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1)=[O:16]>[OH-].[Na+].[Rh]>[CH2:18]([O:17][C:15]([N:1]1[CH:2]([C:10]([OH:12])=[O:11])[CH2:3][CH2:4][CH2:5][CH:6]1[C:7]([OH:9])=[O:8])=[O:16])[C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1

Participants

6

Reactant 3

HCID 962WaterHCID 103672,6-Pyridinedicarboxylic acidHCID 10387Benzyl chloroformate

Product 1

HCID 12265926Piperidine-1,2,6-tricarboxylic acid 1-benzyl esterYield 83.1%

Reagents, catalysts & solvents 2

HCID 23948RhodiumCatalystHCID 14798Sodium HydroxideSolvent

Conditions

Temperature
0 °C

Procedure

2,6-Pyridine dicarboxylic acid (25 g, 0.15 mol) was dissolved in 2.0M NaOH (154 mL) and H2O (30 mL) at room temperature, and placed in a 500-mL Parr bottle. Rhodium on alumina powder (5%, 1.87 g) was added and the mixture was purged with argon for 15 minutes. The reaction mixture was shaken under 55 psi of hydrogen for 48 hours. The suspension was filtered through compacted Celite, and the clear filtrate was cooled to 0° C. Benzyl chloroformate (30.62 g, 0.18 mol) was added from the top to the cooled filtrate in three portions during a period of 30 minutes, and the solution was allowed to reach room temperature and stirred for additional 5 hours. The remaining benzyl chloroformate was extracted from the mixture with diethyl ether. The aqueous layer was acidified with 2N HCl and extracted with ethyl acetate (EtOAc). The EtOAc was passed over a short plug of Na2SO4 and evaporated. The residue was triturated with EtOAc (20 mL), and the resulting white solid was collected by vacuum filtration, washed with EtOAc (3×20 mL), and air-dried to give Compound 1 (38.3 g, 83% yield). Rf=0.06 (10% MeOH/CHCl3); 1H NMR: δ 1.49-1.73 (m, 4H), 1.96-2.03 (m, 2H), 4.48-4.65 (m, 2H), 5.10 (s, 2H), 7.26-7.35 (m, 5H).

Workup

  1. customat room temperature
  2. customthe mixture was purged with argon for 15 minutes
  3. filtrationThe suspension was filtered
  4. customto reach room temperature
  5. stirringstirred for additional 5 hours
  6. extractionThe remaining benzyl chloroformate was extracted from the mixture with diethyl ether
  7. extractionextracted with ethyl acetate (EtOAc)
  8. customevaporated
  9. customThe residue was triturated with EtOAc (20 mL)
  10. filtrationthe resulting white solid was collected by vacuum filtration
  11. washwashed with EtOAc (3×20 mL)
  12. customair-dried

Sources & evidence

ORD record
ord-406808a37ba44699a81cf4fa70e2858c
Source dataset
uspto-grants-2003_10
Patent number
US06630472B1

Reaction notes

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