Hydrochloric Acid → 1-Carbobenzoxy-4-piperidinecarboxylic Acid

HRID 1020023Notes

Reaction equation

HRID 1020023 reaction equation
[NH:1]1[CH2:6][CH2:5][CH:4]([C:7]([OH:9])=[O:8])[CH2:3][CH2:2]1.[OH-].[Na+].Cl[C:13]([O:15][CH2:16][C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1)=[O:14].C1(C)C=CC=CC=1.Cl>O>[C:13]([N:1]1[CH2:6][CH2:5][CH:4]([C:7]([OH:9])=[O:8])[CH2:3][CH2:2]1)([O:15][CH2:16][C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1)=[O:14]

Participants

7

Reactant 5

HCID 313Hydrochloric AcidHCID 1140TolueneHCID 37734-Piperidinecarboxylic acidHCID 10387Benzyl chloroformateHCID 14798Sodium Hydroxide

Product 1

HCID 7364891-Carbobenzoxy-4-piperidinecarboxylic AcidYield 64%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

To a stirred solution of piperidine-4-carboxylic acid (5.0 g, 38.7 mmol) and NaOH (1.86 g, 46.5 mmol) in H2O (15 ml) was added dropwise a 50% solution of benzyl chloroformate in toluene (13.6 mL, 40.6 mmol) over a period of half an hour at 0° C. The reaction mixture was stirred at room temperature for 6 hours. The progress of the reaction was monitored by TLC. After completion, the reaction mixture was acidified with dil. HCl (pH 3) and extracted with ethyl acetate (3×100 ml). The combined organic phases were dried over sodium sulfate and concentrated. The crude product was purified by flash column chromatography (silica gel, elution with 30% ethyl acetate/n-hexanes) to afford piperidine-1,4-dicarboxylic acid monobenzyl ester (VI) (6.5 g, 64%) as a pale yellow oil.

Workup

  1. extractionextracted with ethyl acetate (3×100 ml)
  2. dry with materialThe combined organic phases were dried over sodium sulfate
  3. concentrationconcentrated
  4. customThe crude product was purified by flash column chromatography (silica gel, elution with 30% ethyl acetate/n-hexanes)

Sources & evidence

ORD record
ord-bc696c9f25f947d484abc6b07901eb0c
Source dataset
uspto-grants-2014_05
Patent number
US08716296B2

Reaction notes

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