N-Methylpiperidine → HCID 54116207, compound

HRID 1900194Notes

Reaction equation

HRID 1900194 reaction equation
CN1CCCCC1.[O:8]([C:15]([NH:17][C@H:18]([C:23]([OH:25])=O)[C@H:19]([CH2:21][CH3:22])[CH3:20])=[O:16])[C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1.ClC(OCC(C)C)=O.[F:34][C:35]1[CH:46]=[CH:45][C:38]([N:39]([CH2:41][CH:42]([NH2:44])[CH3:43])[CH3:40])=[CH:37][CH:36]=1>C(Cl)Cl.O>[F:34][C:35]1[CH:46]=[CH:45][C:38]([N:39]([CH2:41][CH:42]([NH:44][C:23](=[O:25])[C@H:18]([C@H:19]([CH2:21][CH3:22])[CH3:20])[NH:17][C:15]([O:8][C:9]2[CH:10]=[CH:11][CH:12]=[CH:13][CH:14]=2)=[O:16])[CH3:43])[CH3:40])=[CH:37][CH:36]=1

Participants

7

Reactant 4

HCID 12291N-MethylpiperidineHCID 62365Isobutyl chloroformateHCID 18972720HCID 18972720, compoundHCID 23278900HCID 23278900, compound

Product 1

HCID 54116207HCID 54116207, compoundYield 13.9%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
-20 °C

Procedure

1.9 g of N-methylpiperidine was added to a solution containing 4.8 g of N-phenoxycarbonyl-L-isoleucine dissolved in 80 ml of methylene chloride, at -20° C. After the mixture was stirred for 10 minutes at the same temperature, 2.6 g of isobutyl chloroformate was added to the mixture, and stirred for 1 hour at -20° C. 3.5 g of 2-(4-fluoro-N-methylanilino)-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, 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 sodium sulfate and the methylene chloride was removed under reduced pressure. The obtained 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 crystal (yield: 13%).

Workup

  1. additionwas added to the mixture
  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 sodium sulfate
  7. customthe methylene chloride was removed under reduced pressure
  8. customThe obtained crude crystal
  9. customwas purified by column chromatography on silica gel

Sources & evidence

ORD record
ord-01331cd8adec4785b6bf9eca8013a779
Source dataset
uspto-grants-1996_11
Patent number
US05574064

Reaction notes

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