Dicyclohexylcarbodiimide → Fmoc-NH-L-Ile-D-Phe-CH2OH

HRID 1442633Notes

Reaction equation

HRID 1442633 reaction equation
[NH2:1][C@H:2]([CH2:5][C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=1)[CH2:3][OH:4].C1CCC(N=C=NC2CCCCC2)CC1.C1C=CC2N(O)N=NC=2C=1.[CH:37]1[C:49]2[CH:48]([CH2:50][O:51][C:52]([NH:54][C@H:55]([C:60](O)=[O:61])[C@H:56]([CH2:58][CH3:59])[CH3:57])=[O:53])[C:47]3[C:42](=[CH:43][CH:44]=[CH:45][CH:46]=3)[C:41]=2[CH:40]=[CH:39][CH:38]=1>CN(C=O)C>[C:52]([NH:54][C@H:55]([C:60]([NH:1][C@@H:2]([CH2:3][OH:4])[CH2:5][C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=1)=[O:61])[C@H:56]([CH2:58][CH3:59])[CH3:57])([O:51][CH2:50][CH:48]1[C:49]2[C:41](=[CH:40][CH:39]=[CH:38][CH:37]=2)[C:42]2[C:47]1=[CH:46][CH:45]=[CH:44][CH:43]=2)=[O:53]

Participants

6

Reactant 4

HCID 10868DicyclohexylcarbodiimideHCID 757711-HydroxybenzotriazoleHCID 853475phenylalaninol, (R)-HCID 2724629N-Fmoc-L-isoleucine

Product 1

HCID 42632374Fmoc-NH-L-Ile-D-Phe-CH2OHYield 47.2%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
25 °C

Procedure

(R)(+)-2-amino-3-phenyl-1-propanol (427 mg, 2.83 mmol) dissolved in dry DMF (20 mL), stirred under nitrogen, to this stirred mixture at 25° C. DCC (699 mg, 3.39 mmol), HOBt (457 mg, 3.38 mmol) was added with constant stirring. After 10 minutes of stirring N-(9-fluorenylmethoxycarbonyl)-L-isoleucine (1.0 g, 2.83 mmol) was added to the above mixture and then stirred at 25° C. for 14 h. After 14 h white colored crystals precipitated out (DCU), which was filtered. The filterate was checked on TLC (2% MeOH: CH2Cl2) which showed formation of a new compound at higher Rf (0.6), LC/MS also showed molecular ion peak corresponding to the dipeptide 1a with other impurities peaks. The crude product was chromatographed on silica gel (Silica gel 60, 63-200μ) column and eluted with 2% MeOH: CH2Cl2 to give 650 mg of the dipeptide Fmoc-NH-L-Ile-D-Phe-CH2OH (1a) as a white solid. Checked on LC/MS which showed M++1 (487.4) and M++Na (509.2).

Workup

  1. stirringstirred at 25° C. for 14 h
  2. customAfter 14 h white colored crystals precipitated out (DCU), which
  3. filtrationwas filtered
  4. customThe crude product was chromatographed on silica gel (Silica gel 60, 63-200μ) column
  5. washeluted with 2% MeOH

Sources & evidence

ORD record
ord-a8755e4794a24f58bd448e435c920e35
Source dataset
uspto-grants-2010_02
Patent number
US07659244B2

Reaction notes

Loading…