Dimethylformamide → n-[2-(3-Tert-butyl-4-hydroxyphenyl)-1-methylethyl]-2-[n-(n-boc-phenyl-alanyl)-n-methylamino]-3-methylbutanamide

HRID 1383738Notes

Reaction equation

HRID 1383738 reaction equation
[C:1]([C:5]1[CH:6]=[C:7]([CH2:12][CH:13]([NH:15][C:16](=[O:23])[CH:17]([NH:21][CH3:22])[CH:18]([CH3:20])[CH3:19])[CH3:14])[CH:8]=[CH:9][C:10]=1[OH:11])([CH3:4])([CH3:3])[CH3:2].N([C:36]([O:38][C:39]([CH3:42])([CH3:41])[CH3:40])=[O:37])[C@H](C(O)=O)CC1C=CC=CC=1.[CH:43]1[CH:44]=[CH:45][C:46]2N(O)N=[N:49][C:47]=2[CH:48]=1.[CH3:53][CH:54]([CH3:61])N=C=NC(C)C.CN(C=[O:66])C>C(OCC)(=O)C>[C:1]([C:5]1[CH:6]=[C:7]([CH2:12][CH:13]([NH:15][C:16](=[O:23])[CH:17]([N:21]([C:53](=[O:66])[C@H:54]([CH3:61])[N:49]([C:47]2[CH:48]=[CH:43][CH:44]=[CH:45][CH:46]=2)[C:36]([O:38][C:39]([CH3:41])([CH3:40])[CH3:42])=[O:37])[CH3:22])[CH:18]([CH3:19])[CH3:20])[CH3:14])[CH:8]=[CH:9][C:10]=1[OH:11])([CH3:3])([CH3:2])[CH3:4]

Participants

7

Reactant 5

HCID 6228DimethylformamideHCID 12734DiisopropylcarbodiimideHCID 757711-HydroxybenzotriazoleHCID 77857L-Phenylalanine, N-[(1,1-dimethylethoxy)carbonyl]-HCID 21187418N-[2-(3-tert-butyl-4-hydroxyphenyl)-1-methylethyl]-3-methyl-2-(methylamino)butanamide

Product 1

HCID 20668311n-[2-(3-Tert-butyl-4-hydroxyphenyl)-1-methylethyl]-2-[n-(n-boc-phenyl-alanyl)-n-methylamino]-3-methylbutanamide

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Procedure

To a solution of 0.36 g (1.12 mmol) of N-[2-(3-tert-butyl-4-hydroxyphenyl)-l-methylethyl]-3-methyl-2-(methylamino)butanamide, 0.75 g (2.81 mmol) of Boc-Phe-OH and 0.38 g (2.81 mmol) of HOBT in DMF (5 ml), 0.44 ml (2.81 mmol) of DIC was added under cooling with ice. After being stirred at room temperature for 2.5 days, the reaction mixture was diluted with ethyl acetate and washed successively with saturated aqueous NaHCO3, water and saturated brine. The organic layer was dried with anhydrous magnesium sulfate and concentrated under reduced pressure; the resulting residue was subjected to silica gel column chromatography (eluting solvent; chloroform:methanol=80:1) to give N-[2-(3-tert-butyl-4-hydroxyphenyl)-1-methylethyl]-2-[N-(N-Boc-phenyl-alanyl)-N-methylamino]-3-methylbutanamide in 333 mg (52%).

Workup

  1. temperatureunder cooling with ice
  2. washwashed successively with saturated aqueous NaHCO3, water and saturated brine
  3. dry with materialThe organic layer was dried with anhydrous magnesium sulfate
  4. concentrationconcentrated under reduced pressure
  5. washthe resulting residue was subjected to silica gel column chromatography (eluting solvent; chloroform:methanol=80:1)

Sources & evidence

ORD record
ord-581dc2a28990486196642175164477e1
Source dataset
uspto-grants-2001_07
Patent number
US06255285B1

Reaction notes

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