N-Methylpiperidine → N1-[2-(4-cyanophenoxy)-1-methylethyl]-N2-phenoxycarbonyl-L-valinamide

HRID 2394322

Reaction equation

HRID 2394322 reaction equation
CN1C[CH2:6][CH2:5][CH2:4][CH2:3]1.Cl[CH2:9][CH2:10][O:11][C:12]([NH:14][C@H:15]([C:19]([OH:21])=O)[CH:16]([CH3:18])[CH3:17])=[O:13].ClC(OCC(C)C)=O.[C:30]([C:32]1[CH:42]=[CH:41][C:35]([O:36][CH2:37][CH:38]([NH2:40])[CH3:39])=[CH:34][CH:33]=1)#[N:31]>C(Cl)Cl.O>[C:30]([C:32]1[CH:42]=[CH:41][C:35]([O:36][CH2:37][CH:38]([NH:40][C:19](=[O:21])[C@H:15]([CH:16]([CH3:17])[CH3:18])[NH:14][C:12]([O:11][C:10]2[CH:9]=[CH:6][CH:5]=[CH:4][CH:3]=2)=[O:13])[CH3:39])=[CH:34][CH:33]=1)#[N:31]

Participants

7

Reactant 4

HCID 12291N-MethylpiperidineHCID 62365Isobutyl chloroformateHCID 189727992-(4-Cyanophenoxy)-1-methylethylamineHCID 54269051N-(2-chloroethoxycarbonyl)-L-valine

Product 1

HCID 53713420N1-[2-(4-cyanophenoxy)-1-methylethyl]-N2-phenoxycarbonyl-L-valinamideYield 52%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
-20 °C

Procedure

0.5 g of N-methylpiperidine was added to a solution containing 1.1 g of N-(2-chloroethoxycarbonyl)-L-valine dissolved in 40 ml of methylene chloride, at -20° C. After the mixture was stirred for 15 minutes at the same temperature, 0.7 g of isobutyl chloroformate was added to the mixture at -40° C., and subsequently the whole mixture was stirred for 1 hour at -20° C. 0.9 g of 2-(4-cyanophenoxy)-1-methylethylamine 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. The whole mixture 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, which was an oily substance, was purified by column chromatography on silica gel, thus yielding 1.0 g of the desired product in the form of colorless grains (yield: 52%).

Workup

  1. additionwas added to the mixture at -40° C.
  2. temperaturewarm naturally to room temperature
  3. stirringwhile being stirred
  4. stirringThe whole mixture was 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. customwas purified by column chromatography on silica gel

Sources & evidence

ORD record
ord-f7a955bc8404499698dbe943abca3d53
Source dataset
uspto-grants-1998_09
Patent number
US05811424

Linked notes

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