N-Methylpiperidine → N-(t-butoxycarbonyl)-L-valine 4-methoxy-1-phenylethylamide

HRID 439745

Reaction equation

HRID 439745 reaction equation
CN1CCCCC1.[C:8]([O:12][C:13]([NH:15][C@H:16]([C:20]([OH:22])=O)[CH:17]([CH3:19])[CH3:18])=[O:14])([CH3:11])([CH3:10])[CH3:9].ClC(OCC(C)C)=O.[CH3:31][O:32][C:33]1[CH:38]=[CH:37][C:36]([CH:39]([NH2:41])[CH3:40])=[CH:35][CH:34]=1>C(Cl)Cl>[CH3:31][O:32][C:33]1[CH:38]=[CH:37][C:36]([CH:39]([NH:41][C:20](=[O:22])[C@H:16]([CH:17]([CH3:18])[CH3:19])[NH:15][C:13]([O:12][C:8]([CH3:9])([CH3:10])[CH3:11])=[O:14])[CH3:40])=[CH:35][CH:34]=1

Participants

6

Reactant 4

HCID 12291N-MethylpiperidineHCID 62365Isobutyl chloroformateHCID 83693Boc-L-ValineHCID 2381811-(4-Methoxyphenyl)ethanamine

Product 1

HCID 14774435N-(t-butoxycarbonyl)-L-valine 4-methoxy-1-phenylethylamideYield 217.1%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
-60 °C

Procedure

2.3 g (0.023 mol) of N-methylpiperidine are added to 5.0 g of t-butoxycarbonyl-L-valine (0.023 mol), dissolved in 50 ml of CH2Cl2, at -20° C. 3.2 g (0.023 mol) of isobutyl chloroformate are then rapidly added dropwise at -20° C., the mixture is subsequently stirred at the same temperature for 10 minutes and cooled to -60° C. and 3.5 g (0.023 mol) of 4-methoxy-1-phenylethylamine are allowed to run in, the temperature being kept below -15° C. After 2 hours at -15° C., the mixture is subsequently stirred at room temperature for 15 hours, the solid is filtered off and rinsed with CH2Cl2, the filtrate is concentrated, the residue is introduced into water, the mixture is extracted twice with ethyl acetate and the combined ethyl acetate phases are washed with NaHCO3 solution and water, dried and concentrated. 17.5 g (85% of theory) of N-(t-butoxycarbonyl)-L-valine 4-methoxy-1-phenylethylamide of melting point 126°-127° C. are obtained.

Workup

  1. custombeing kept below -15° C
  2. waitAfter 2 hours at -15° C.
  3. stirringthe mixture is subsequently stirred at room temperature for 15 hours
  4. filtrationthe solid is filtered off
  5. washrinsed with CH2Cl2
  6. concentrationthe filtrate is concentrated
  7. additionthe residue is introduced into water
  8. extractionthe mixture is extracted twice with ethyl acetate
  9. washthe combined ethyl acetate phases are washed with NaHCO3 solution and water
  10. customdried
  11. concentrationconcentrated

Sources & evidence

ORD record
ord-836d11ad9b7c41dea4121f53b7b7fa49
Source dataset
uspto-grants-1996_05
Patent number
US05516786

Linked notes

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