Citric Acid → BocDTrp-LeuOH

HRID 2418578Notes

Reaction equation

HRID 2418578 reaction equation
[NH2:1][C@H:2]([C:7]([OH:9])=[O:8])[CH2:3][CH:4]([CH3:6])[CH3:5].[OH-].[K+].[NH:12]([C:34]([O:36][C:37]([CH3:40])([CH3:39])[CH3:38])=[O:35])[C@@H:13]([C:24](ON1C(=O)CCC1=O)=[O:25])[CH2:14][C:15]1[C:23]2[C:18](=[CH:19][CH:20]=[CH:21][CH:22]=2)[NH:17][CH:16]=1.C(O)(=O)CC(CC(O)=O)(C(O)=O)O>CN(C)C=O.O.CCOCC>[NH:12]([C:34]([O:36][C:37]([CH3:40])([CH3:39])[CH3:38])=[O:35])[C@@H:13]([C:24]([NH:1][C@H:2]([C:7]([OH:9])=[O:8])[CH2:3][CH:4]([CH3:6])[CH3:5])=[O:25])[CH2:14][C:15]1[C:23]2[C:18](=[CH:19][CH:20]=[CH:21][CH:22]=2)[NH:17][CH:16]=1

Participants

8

Reactant 4

HCID 311Citric AcidHCID 6106L-LeucineHCID 14797Potassium HydroxideHCID 51340392Boc-D-tryptophan N-hydroxysuccinimide ester

Product 1

HCID 131713760BocDTrp-LeuOHYield 74%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 3283Diethyl EtherSolventHCID 6228DimethylformamideSolvent2×

Procedure

Solutions of leucine (90.0 mmole.) in dimethylformamide (150 ml.) and potassium hydroxide (90.0 mmole.) in water (25 ml.) were combined and chilled in an ice-salt bath. A chilled mixture of BocDTrpOSu (89.7 mmole.) in dimethylformamide (100 ml.) was then added. The mixture was stirred for one hour at the ice-salt bath temperature, allowed to warm to room temperature overnight, and distributed between aqueous citric acid (5%) and ether. The aqueous layer was extracted twice more with ether. The ethereal extracts were combined and dried over magnesium sulfate. The product precipitated from the ether onto the drying agent. Ether was removed from the mixture. Extraction of the solids with methanol, removal of the methanol and recrystallization of the residue from methanol-water afforded BocDTrp-LeuOH in 74% yield (27.85 g., m.r. 187°-190° C.).

Workup

  1. temperaturechilled in an ice-salt bath
  2. additionwas then added
  3. extractionThe aqueous layer was extracted twice more with ether
  4. dry with materialdried over magnesium sulfate
  5. customThe product precipitated from the ether onto the drying agent
  6. customEther was removed from the mixture
  7. extractionExtraction of the solids
  8. customwith methanol, removal of the methanol and recrystallization of the residue from methanol-water

Sources & evidence

ORD record
ord-aab023c19403496983a9540591b39294
Source dataset
uspto-grants-1984_09
Patent number
US04472305

Reaction notes

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