Trifluoroacetic acid → HCID 131720345, compound

HRID 431409Notes

Reaction equation

HRID 431409 reaction equation
[C:1]([NH:8][C@H:9]([C:14]([OH:16])=[O:15])[CH2:10][CH:11]([CH3:13])[CH3:12])([O:3][C:4]([CH3:7])(C)C)=[O:2].[CH3:17][N:18]([O:27][CH3:28])[C:19](=[O:26])[C@H:20]([CH2:22][CH:23]([CH3:25])[CH3:24])[NH2:21].FC(F)(F)C(O)=O>C(Cl)Cl>[CH3:13][CH:11]([CH2:10][C@H:9]([NH:8][C:1]([O:3][CH2:4][C:7]1[CH:24]=[CH:23][CH:22]=[CH:20][CH:19]=1)=[O:2])[C:14]([OH:16])=[O:15])[CH3:12].[NH2:8][C@H:9]([C:14]([OH:16])=[O:15])[CH2:10][CH:11]([CH3:13])[CH3:12].[CH3:17][N:18]([O:27][CH3:28])[C:19](=[O:26])[C@H:20]([CH2:22][CH:23]([CH3:25])[CH3:24])[NH2:21]

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 131720343HCID 131720343, compound

Product 1

HCID 131720345HCID 131720345, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

A solution of N-Boc-L-leucine-L-leucine N,O-dimethylhydroxylamide (923 mg) and trifluoroacetic acid (10 mL) in methylene chloride (20 mL) was stirred at 0° C. for 3 hours. The solvent was evaporated under reduced pressure and the residue was dried under vacuum. A portion of this product (488 mg) was transferred to another flask and was combined with Z-L-leucine (451 mg), 1-hydroxybenzotriazole monohydrate (276 mg), N-methylmorpholine (0.22 mL), and DMF (15 mL). 1-Ethyl-3-(3-dimethylaminopropyl) carbodiimide hydrochloride (357 mg) was then added at 0° C. The mixture was stirred at 0° C. for 2 h, then at room temperature for 42 h. The reaction was quenched with water (50 mL) and the mixture was extracted with EtOAc (3×60 mL). The combined organic layers were washed with aqueous 10% HCl, saturated NaHCO3, and brine, then dried over anhydrous MgSO4, filtered, and evaporated to afford the product as a white solid. This was further purified by silica gel chromatography (hexane/acetone 80:20, 70:30) to give the title compound (546 mg) as a white solid.

Workup

  1. customThe solvent was evaporated under reduced pressure
  2. customthe residue was dried under vacuum
  3. customA portion of this product (488 mg) was transferred to another flask
  4. addition1-Ethyl-3-(3-dimethylaminopropyl) carbodiimide hydrochloride (357 mg) was then added at 0° C
  5. waitat room temperature for 42 h
  6. customThe reaction was quenched with water (50 mL)
  7. extractionthe mixture was extracted with EtOAc (3×60 mL)
  8. washThe combined organic layers were washed with aqueous 10% HCl, saturated NaHCO3, and brine
  9. dry with materialdried over anhydrous MgSO4
  10. filtrationfiltered
  11. customevaporated

Sources & evidence

ORD record
ord-f20a29b70f2d4adb9786dd6a3282b115
Source dataset
uspto-grants-2003_12
Patent number
US06660268B1

Reaction notes

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