Water → Boc-D-Tyr(Me)-L-Ile-DL-Pip-OBzl

HRID 1444154Notes

Reaction equation

HRID 1444154 reaction equation
[C:1]([OH:7])([C:3](F)(F)F)=[O:2].[NH:8](C(OC(C)(C)C)=O)[C@H:9]([C:14]([N:16]1C[CH2:30][CH2:29][CH2:28][CH:17]1C(OCC1C=CC=CC=1)=O)=[O:15])[C@H:10]([CH2:12][CH3:13])[CH3:11].[NH:39]([C:53]([O:55][C:56]([CH3:59])([CH3:58])[CH3:57])=[O:54])[C@@H:40]([C:50]([OH:52])=O)[CH2:41][C:42]1[CH:47]=[CH:46][C:45]([O:48][CH3:49])=[CH:44][CH:43]=1.[CH:60]1[CH:61]=[CH:62][C:63]2N(O)N=N[C:64]=2[CH:65]=1.O.[CH3:71]N(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(CC)CC>CN(C=O)C>[NH:39]([C:53]([O:55][C:56]([CH3:59])([CH3:58])[CH3:57])=[O:54])[C@@H:40]([C:50]([NH:8][C@H:9]([C:14]([N:16]1[CH2:17][CH2:28][CH2:29][CH2:30][CH:3]1[C:1]([O:7][CH2:71][C:64]1[CH:63]=[CH:62][CH:61]=[CH:60][CH:65]=1)=[O:2])=[O:15])[C@H:10]([CH2:12][CH3:13])[CH3:11])=[O:52])[CH2:41][C:42]1[CH:43]=[CH:44][C:45]([O:48][CH3:49])=[CH:46][CH:47]=1

Participants

9

Reactant 7

HCID 962WaterHCID 6422Trifluoroacetic acidHCID 8471TriethylamineHCID 757711-HydroxybenzotriazoleHCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 7017908Boc-O-methyl-D-tyrosineHCID 131724669Boc-L-Ile-DL-Pip-OBzl

Product 1

HCID 131727274Boc-D-Tyr(Me)-L-Ile-DL-Pip-OBzl

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

TFA (4 mL) was added to Boc-L-Ile-DL-Pip-OBzl (2.64 g, 6.1 mmol) under ice-cold conditions, and this was left to stand for 30 minutes. TFA was removed by evaporation, then Boc-D-Tyr(Me)-OH (2.16 g, 7.3 mmol) and HOBt.H2O (1.40 g, 9.15 mmol) were added, and this mixture was dissolved in DMF (10 mL). While cooling on ice, HBTU (3.47 g, 9.15 mmol) and Et3N (3.51 ml, 25 mmol) were added to the solution, and this was stirred for 1 hour. The reaction solution was concentrated, and the residue was extracted with ethyl acetate. The extract was washed 3 times each with 10% aqueous citric acid solution, 4% aqueous sodium bicarbonate solution, and saturated brine, and dried over magnesium sulfate, and then ethyl acetate was removed by evaporation. Purification of the residue by silica gel chromatography yielded the desired product as a foam (column: Merck Kieselgel 60 Φ 5.0×12 cm, eluent: CHCl3/MeOH, 99/1). TLC: Rf, 0.75 (CHCl3/MeOH, 9/1). Yield: 2.45 g (4.02 mmol, 66%).

Workup

  1. waitthis was left
  2. customTFA was removed by evaporation
  3. additionwere added to the solution
  4. concentrationThe reaction solution was concentrated
  5. extractionthe residue was extracted with ethyl acetate
  6. washThe extract was washed 3 times each with 10% aqueous citric acid solution, 4% aqueous sodium bicarbonate solution, and saturated brine
  7. dry with materialdried over magnesium sulfate
  8. customethyl acetate was removed by evaporation
  9. customPurification of the residue by silica gel chromatography

Sources & evidence

ORD record
ord-5d5f74b658e24ac79e2f225a982fff34
Source dataset
uspto-grants-2010_02
Patent number
US07662778B2

Reaction notes

Loading…