Citric Acid → HCID 14336499, compound

HRID 373392Notes

Reaction equation

HRID 373392 reaction equation
O.[C:2]([NH:9][C@@H:10]([C:15]([OH:17])=O)[CH2:11][CH:12]([CH3:14])[CH3:13])([O:4][C:5]([CH3:8])([CH3:7])[CH3:6])=[O:3].C1(C)C=CC(S(O)(=O)=O)=CC=1.[CH2:29]([O:36][C:37](=[O:43])[C@H:38]([CH:40]([CH3:42])[CH3:41])[NH2:39])[C:30]1[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=1.ON1C2C=CC=CC=2N=N1.C(N(CC)CC)C.Cl(O)(=O)(=O)=O.C(N=C=NCCCN(C)C)C.C(O)(=O)CC(CC(O)=O)(C(O)=O)O>ClCCl.O>[CH2:29]([O:36][C:37](=[O:43])[C@H:38]([CH:40]([CH3:41])[CH3:42])[NH:39][C:15](=[O:17])[C@@H:10]([CH2:11][CH:12]([CH3:13])[CH3:14])[NH:9][C:2]([O:4][C:5]([CH3:6])([CH3:7])[CH3:8])=[O:3])[C:30]1[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=1

Participants

9

Reactant 6

HCID 311Citric AcidHCID 8471TriethylamineHCID 757711-HydroxybenzotriazoleHCID 2724763BOC-D-LEU-OH H2OHCID 11567066O-benzyl-L-valine toluene-p-sulphonateHCID 18959840HCID 18959840, compound

Product 1

HCID 14336499HCID 14336499, compoundYield 110.2%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent

Procedure

0.749 g (3.00 mmol) of Boc-D-leucine monohydrate, 1.252 g (3.30 mmol) of L-valine benzyl ester p-toluenesulfonate and 0.811 g (6.00 mmol) of N-hydroxybenzotriazole were dissolved in 15 ml of dichloromethane. The resulting mixture was cooled with ice, and admixed with 0.504 ml (3.60 mmol) of triethylamine and 1.108 g (4.20 mmol) of 97% 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide perchlorate. The reaction mixture was stirred for 2 hours, and then further stirred at room temperature for 4 hours. After the completion of the reaction, 30 ml of water and 5 ml of a 1% aqueous citric acid solution were added to the reaction mixture. The crystals thus deposited were filtered off. The organic layer successively was washed with 20 ml of water, 20 ml of a saturated aqueous sodium hydrogen carbonate solution and 10 ml of water, dried over anhydrous sodium sulfate, and distilled to remove the solvent therefrom, whereby 1.390 g of crude Boc-D-leucyl-L-valine benzyl ester product were obtained as white crystals.

Workup

  1. temperatureThe resulting mixture was cooled with ice
  2. stirringfurther stirred at room temperature for 4 hours
  3. additionwere added to the reaction mixture
  4. filtrationThe crystals thus deposited were filtered off
  5. washThe organic layer successively was washed with 20 ml of water, 20 ml of a saturated aqueous sodium hydrogen carbonate solution and 10 ml of water
  6. dry with materialdried over anhydrous sodium sulfate
  7. distillationdistilled
  8. customto remove the solvent

Sources & evidence

ORD record
ord-c2907bbe056e4674bccabd51ce6b7734
Source dataset
uspto-grants-1992_11
Patent number
US05162500

Reaction notes

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