Triethylamine → 1-Piperidinecarboxylic acid, 4-(aminocarbonyl)-4-phenyl-, 1,1-dimethylethyl ester

HRID 1682963Notes

Reaction equation

HRID 1682963 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][C:11]([C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)([C:14](O)=[O:15])[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].C([N:25](CC)CC)C.C(OC(Cl)=O)C(C)C>C1COCC1>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][C:11]([C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)([C:14]([NH2:25])=[O:15])[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 62365Isobutyl chloroformateHCID 7369171-((Tert-butoxy)carbonyl)-4-phenylpiperidine-4-carboxylic acid

Product 1

HCID 227418011-Piperidinecarboxylic acid, 4-(aminocarbonyl)-4-phenyl-, 1,1-dimethylethyl ester

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-10 °C

Procedure

1-tert-Butoxycarbonyl-4-phenyl-piperidine-4-carboxylic acid (1.22 g, 4 mmol) was combined with THF (40 mL) and cooled to -10° C. Triethylamine (0.61 mL, 4.4 mmol, 1.1 eq.) and isobutylchloroformate (0.57 mL, 4.4 mmol, 1.1 eq.) were added and the reaction was allowed to warm to ambient temperature and stir 15 h. The slurry was filtered and the solids were rinsed with THF. The filtrate was cooled to -10° C. and sparged with NH3 (gas) for 0.5 h. The slurry was allowed to warm to 20° C. and stir for 15 h. The slurry was filtered and the filtrate was diluted with ethyl acetate and washed with saturated NaHCO3 (3X). The organic phase was dried over MgSO4, filtered, and concentrated in vacuo to give a residue. The residue was recrystallized from diethyl ether to give the title compound:

Workup

  1. temperatureto warm to ambient temperature
  2. filtrationThe slurry was filtered
  3. washthe solids were rinsed with THF
  4. temperatureThe filtrate was cooled to -10° C.
  5. customsparged with NH3 (gas) for 0.5 h
  6. temperatureto warm to 20° C.
  7. stirringstir for 15 h
  8. filtrationThe slurry was filtered
  9. additionthe filtrate was diluted with ethyl acetate
  10. washwashed with saturated NaHCO3 (3X)
  11. dry with materialThe organic phase was dried over MgSO4
  12. filtrationfiltered
  13. concentrationconcentrated in vacuo
  14. customto give a residue
  15. customThe residue was recrystallized from diethyl ether

Sources & evidence

ORD record
ord-468f8747b02744dbb80f99592a09fdcb
Source dataset
uspto-grants-1997_06
Patent number
US05635510

Reaction notes

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