Sodium Hydroxide → 1-[(Benzyloxy)carbonyl]-4-methylpiperidine-4-carboxylic acid

HRID 2354052Notes

Reaction equation

HRID 2354052 reaction equation
C([O:3][C:4]([C:6]1([CH3:19])[CH2:11][CH2:10][N:9]([C:12]([O:14][C:15]([CH3:18])(C)C)=[O:13])[CH2:8][CH2:7]1)=[O:5])C.[OH-].[Na+].O=C1CCC(=O)N1OC(=O)OC[C:33]1[CH:38]=[CH:37]C=[CH:35][CH:34]=1>Cl>[CH2:15]([O:14][C:12]([N:9]1[CH2:8][CH2:7][C:6]([CH3:19])([C:4]([OH:3])=[O:5])[CH2:11][CH2:10]1)=[O:13])[C:18]1[CH:37]=[CH:38][CH:33]=[CH:34][CH:35]=1

Participants

5

Reactant 3

HCID 14798Sodium Hydroxide2×HCID 83172Benzyl succinimido carbonateHCID 162182761-tert-Butyl 4-ethyl 4-methylpiperidine-1,4-dicarboxylate

Product 1

HCID 178959881-[(Benzyloxy)carbonyl]-4-methylpiperidine-4-carboxylic acid

Reagents, catalysts & solvents 1

HCID 313Hydrochloric AcidSolvent

Conditions

Temperature
0 °C

Procedure

4-Methyl-piperidine-1,4-dicarboxylic acid 1-tert-butyl ester 4-ethyl ester (2.71 g, 10 mmol) is heated with 6M aq. HCl (20 mL) at 95° C. for 2 days. The mixture is cooled, basified with 33% aq. NaOH (ice bath cooling) and extracted with ether (2×50 mL). A spatula of NaH2PO4 is added, then the pH adjusted to 7 with conc. aq. HCl, CH2Cl2 (50 Vol %) is added and the mixture cooled at 0° C. Carbonic acid benzyl ester 2,5-dioxo-pyrrolidin-1-yl ester (1.508 g, 5 mmol) is added to the strongly stirred biphasic system and the mixture is stirred for 2 h. The pH is adjusted to 14 with aq. NaOH (1M) and the phases are separated. The aq. phase is extracted with CH2Cl2 (2×50 mL), the organic extracts are discarded. The pH is adjusted to 2 and the mixture is extracted with CHCl3 (4×50 mL). The organic extracts are dried (Na2SO4), filtered and evaporated to provide the title compound.

Workup

  1. temperatureThe mixture is cooled
  2. extractionextracted with ether (2×50 mL)
  3. additionA spatula of NaH2PO4 is added
  4. additionis added
  5. customthe phases are separated
  6. extractionThe aq. phase is extracted with CH2Cl2 (2×50 mL)
  7. extractionthe mixture is extracted with CHCl3 (4×50 mL)
  8. dry with materialThe organic extracts are dried (Na2SO4)
  9. filtrationfiltered
  10. customevaporated

Sources & evidence

ORD record
ord-35623fe06e8346a7aebc28fedbf25351
Source dataset
uspto-grants-2010_07
Patent number
US07750161B2

Reaction notes

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