N-Methylpiperidine → N-isopropoxycarbonyl-L-valyl-N-(4-cyanophenyl)glycinamide

HRID 1900206Notes

Reaction equation

HRID 1900206 reaction equation
CN1CCCCC1.[CH:8]([O:11][C:12]([NH:14][C@H:15]([C:19]([OH:21])=O)[CH:16]([CH3:18])[CH3:17])=[O:13])([CH3:10])[CH3:9].ClC(OCC(C)C)=O.[C:30]([C:32]1[CH:37]=[CH:36][C:35]([NH:38][C:39](=[O:42])[CH2:40][NH2:41])=[CH:34][CH:33]=1)#[N:31]>C(Cl)Cl.O>[CH:8]([O:11][C:12]([NH:14][C@H:15]([C:19]([NH:41][CH2:40][C:39]([NH:38][C:35]1[CH:36]=[CH:37][C:32]([C:30]#[N:31])=[CH:33][CH:34]=1)=[O:42])=[O:21])[CH:16]([CH3:17])[CH3:18])=[O:13])([CH3:9])[CH3:10]

Participants

7

Reactant 4

HCID 12291N-MethylpiperidineHCID 62365Isobutyl chloroformateHCID 11063514(2S)-3-methyl-2-(((propan-2-yloxy)carbonyl)amino)butanoic acidHCID 187889462-amino-N-(4-cyanophenyl)acetamide

Product 1

HCID 67638785N-isopropoxycarbonyl-L-valyl-N-(4-cyanophenyl)glycinamideYield 48.6%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
-20 °C

Procedure

0.3 g of N-methylpiperidine was added to a solution containing 0.6 g of N-isopropoxycarbonyl-L-valine dissolved in 40 ml of methylene chloride, at -20° C. After the mixture was stirred for 10 minutes at the same temperature, 0.4 g of isobutyl chloroformate was added to the n-fixture, and stirred for 1 hour at -20° C. 0.5 g of N1 -(4-cyanophenyl)glycinamide was added to this mixture at -60° C., and then the reaction mixture was allowed to sit and warm naturally to room temperature while being stirred, and was stirred for 20 hours at room temperature. Water was subsequently added to the reaction mixture. After the methylene chloride layer was washed successively with a 5% aqueous solution of sodium bicarbonate and water, the organic layer was dried over anhydrous magnesium sulfate and the methylene chloride was removed under reduced pressure. The residue was purified by column chromatography on silica gel, thus obtaining 0.5 g of the desired product in the form of colorless powder (yield: 49%).

Workup

  1. additionwas added to the n-fixture
  2. temperaturewarm naturally to room temperature
  3. stirringwhile being stirred
  4. stirringwas stirred for 20 hours at room temperature
  5. washAfter the methylene chloride layer was washed successively with a 5% aqueous solution of sodium bicarbonate and water
  6. dry with materialthe organic layer was dried over anhydrous magnesium sulfate
  7. customthe methylene chloride was removed under reduced pressure
  8. customThe residue was purified by column chromatography on silica gel

Sources & evidence

ORD record
ord-c0c2d90151594b849f00f86a58919815
Source dataset
uspto-grants-1996_11
Patent number
US05574064

Reaction notes

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