Dimethylformamide → Fmoc-glycylglycine-4,4'-dimethoxytrityloxybutylamide

HRID 1478983Notes

Reaction equation

HRID 1478983 reaction equation
[C:1]([NH:18][CH2:19][C:20]([NH:22][CH2:23][C:24](O)=[O:25])=[O:21])([O:3][CH2:4][CH:5]1[C:17]2[C:12](=[CH:13][CH:14]=[CH:15][CH:16]=2)[C:11]2[C:6]1=[CH:7][CH:8]=[CH:9][CH:10]=2)=[O:2].C1(N=C=NC2CCCCC2)CCCCC1.O.ON1C2C=CC=CC=2N=N1.[CH3:53][O:54][C:55]1[CH:81]=[CH:80][C:58]([C:59]([O:74][CH2:75][CH2:76][CH2:77][CH2:78][NH2:79])([C:68]2[CH:73]=[CH:72][CH:71]=[CH:70][CH:69]=2)[C:60]2[CH:65]=[CH:64][C:63](OC)=[CH:62][CH:61]=2)=[CH:57][CH:56]=1.CN(C)[CH:84]=[O:85]>>[CH3:84][O:85][CH:75]([O:74][C:59]([C:60]1[CH:61]=[CH:62][CH:63]=[CH:64][CH:65]=1)([C:58]1[CH:80]=[CH:81][C:55]([O:54][CH3:53])=[CH:56][CH:57]=1)[C:68]1[CH:73]=[CH:72][CH:71]=[CH:70][CH:69]=1)[CH2:76][CH2:77][CH2:78][NH:79][C:24](=[O:25])[CH2:23][NH:22][C:20](=[O:21])[CH2:19][NH:18][C:1]([O:3][CH2:4][CH:5]1[C:6]2[C:11](=[CH:10][CH:9]=[CH:8][CH:7]=2)[C:12]2[C:17]1=[CH:16][CH:15]=[CH:14][CH:13]=2)=[O:2]

Participants

6

Reactant 5

HCID 6228Dimethylformamide2×HCID 10868DicyclohexylcarbodiimideHCID 27960291-Hydroxybenzotriazole hydrateHCID 7019069Fmoc-Gly-Gly-OHHCID 713750964-[Bis(4-methoxyphenyl)(phenyl)methoxy]butan-1-amine

Product 1

HCID 131736539Fmoc-glycylglycine-4,4'-dimethoxytrityloxybutylamideYield 68%

Procedure

To a solution (70 ml) of Fmoc-glycylglycine (Fmoc-GlyGly-OH, purchased from China Langchem) (2.50 g, 7.05 mmol), dicyclohexylcarbodiimide (1.75 g, 8.46 mmol) and 1-hydroxybenzotriazole monohydrate (2.59 g, 16.92 mmol) in anhydrous N,N-dimethylformamide was added a solution (50 ml) of compound 12 (3.31 g, 8.46 mmol) in anhydrous N,N-dimethylformamide under ice-cooling under an argon atmosphere. After removing the ice bath, the mixture was stirred at room temperature overnight under an argon atmosphere. The resulting precipitate was filtered off, and the filtrate was concentrated at 35° C. under reduced pressure. To the obtained residue was added dichloromethane (200 ml), and the mixture was washed twice with saturated brine. The organic layer was fractionated, dried over sodium sulfate, and the solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography (eluent: dichloromethane-methanol (95:5)+0.05% pyridine, and then dichloromethane-methanol (9:1)+0.05% pyridine) to give Fmoc-glycylglycine-4,4′-dimethoxytrityloxybutylamide (13) (3.49 g, 68%) as a colorless syrup.

Workup

  1. temperaturecooling under an argon atmosphere
  2. customAfter removing the ice bath
  3. filtrationThe resulting precipitate was filtered off
  4. concentrationthe filtrate was concentrated at 35° C. under reduced pressure
  5. additionTo the obtained residue was added dichloromethane (200 ml)
  6. washthe mixture was washed twice with saturated brine
  7. dry with materialdried over sodium sulfate
  8. customthe solvent was evaporated under reduced pressure
  9. customThe residue was purified by silica gel column chromatography (eluent

Sources & evidence

ORD record
ord-716e83aa51264e5db6004502692bcb95
Source dataset
uspto-grants-2016_08
Patent number
US09404108B2

Reaction notes

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