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

HRID 1900172

Reaction equation

HRID 1900172 reaction equation
CN1CCCCC1.[O:8]([C:15]([NH:17][C@H:18]([C:22]([OH:24])=O)[CH:19]([CH3:21])[CH3:20])=[O:16])[C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1.ClC(OCC(C)C)=O.[C:33]([C:35]1[CH:45]=[CH:44][C:38]([O:39][CH2:40][CH:41]([NH2:43])[CH3:42])=[CH:37][CH:36]=1)#[N:34]>C(Cl)Cl.O>[C:33]([C:35]1[CH:45]=[CH:44][C:38]([O:39][CH2:40][CH:41]([NH:43][C:22](=[O:24])[C@H:18]([CH:19]([CH3:20])[CH3:21])[NH:17][C:15]([O:8][C:9]2[CH:10]=[CH:11][CH:12]=[CH:13][CH:14]=2)=[O:16])[CH3:42])=[CH:37][CH:36]=1)#[N:34]

Participants

7

Reactant 4

HCID 12291N-MethylpiperidineHCID 62365Isobutyl chloroformateHCID 9816135N-Phenoxycarbonyl-L-valineHCID 189727992-(4-Cyanophenoxy)-1-methylethylamine

Product 1

HCID 53713420N1-[2-(4-cyanophenoxy)-1-methylethyl]-N2-phenoxycarbonyl-L-valinamideYield 22.3%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
-20 °C

Procedure

1.3 g of N-methylpiperidine was added to a solution containing 3 g of N-phenoxycarbonyl-L-valine dissolved in 50 mL of methylene chloride, at -20° C. After the mixture was stirred for 10 minutes at the same temperature, 1.7 g of isobutyl chloroformate was added to the mixture at -40° C., and stirred for 1 hour at -20° C. 2.2 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, with stirring, and 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 a crude crystal, was purified by column chromatography on silica gel, thus obtaining 1.1 g of the desired product in the form of a white powder (yield: 22%).

Workup

  1. additionwas added to the mixture at -40° C.
  2. temperaturewarm naturally to room temperature
  3. stirringwith stirring
  4. stirringstirred 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-497cf125844f40ebbebae9bb5f7aa4c3
Source dataset
uspto-grants-1996_11
Patent number
US05574064

Linked notes

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