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

Participants

Reaction Conditions

Reaction Steps

Dipeptide Fmoc-NH-L-Ile-D-Phe-CH2OH (1a) (520 mg, 1.06 mmol) was taken in 20% piperidine in DMF (2 mL) and stirred for 15 minutes at 25° C., TLC examination showed complete removal of the Fmoc protecting group (NH2-L-Ile-D-Phe-CH2OH), further confirmed by LC/MS examination, which showed M+−1 (263.3) peak. The reaction mixture was concentrated in vacuo, excess of the piperidine was removed by co-evaporating with toluene (2×10 mL), the free amino dipeptide was further dried over high vacumn for 30 minutes, and then redissolved in dry DMF (2 mL) and added to the mixture of N-(9-fluorenylmethoxycarbonyl)-L-leucine (38.1 mg, 1.06 mmol), DCC (262.0 mg, 1.27 mmol) and HOBt (171.4 mg, 1.27 mmol) in dry DMF (20 mL) at 25° C. The stirring was further continued for 14 h at 25° C. After 14 h white colored crystals precipitated out (DCU), which was filtered. The filterate was checked on TLC (3% MeOH: CH2Cl2) which showed formation of a new compound at higher Rf (0.5), LC/MS also showed molecular ion peak corresponding to the tripeptide 2a with other impurities peaks. The crude product was chromatographed on silica gel (Silica gel 60, 63-200μ) column and eluted with 3% MeOH: CH2Cl2 to give 310 mg of the tripeptide Fmoc-NH-L-Leu-L-Ile-D-Phe-CH2OH (2a) as a white solid. Checked on LC/MS which showed M++1 (600.3) and M++Na (622.3).

Provenance & Evidence