Reaction #969862

Reaction equation

diisopropyl ethyl amine

Z-Glu(OtBu)-OH

hydroxybenzotriazole

H-Gly-GlyNH2

N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride

→

title compound

Yield 86.2%

Z-Glu(OtBu)-Gly-Gly-NH2

Yield 86.2%

Solvents

Dimethyl formamide

Conditions

Workup

1. 1
   OtherThe reaction mixture was purified in three equal portions by direct injection on a preparative 5 cm×25 cm C18 HPLC column
2. 2
   workup.WAITfollowed by a 15 min linear gradient from 5% acetonitrile to 90% acetonitrile
3. 3
   Othersolvent was removed by rotary evaporation under vacuum

Procedure

40 mL of Dimethyl formamide was added to 2.52 g (7.47 mmol) of Z-Glu(OtBu)-OH, 1.3 g (8.49 mmol) of hydroxybenzotriazole, 1.3 g (7.76 mmol) of H-Gly-GlyNH2, and 1.52 g (7.93 mmol) of N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride. 2.5 mL (14.3 mmol) of diisopropyl ethyl amine was added and the reaction was stirred over night. The reaction mixture was purified in three equal portions by direct injection on a preparative 5 cm×25 cm C18 HPLC column. The column was run at 100 mL/min with deionized water containing 0.3% formic acid with 5% acetonitrile for 10 min followed by a 15 min linear gradient from 5% acetonitrile to 90% acetonitrile. Product fractions (retention time 18-20 min) were combined and solvent was removed by rotary evaporation under vacuum to give 2.9 g (83%) of the title compound. 1H NMR (400 MHz, CDCl3) δ 7.79-7.68 (m, 1H), 7.64 (s, 1H), 7.27 (q, J=4.9, 5H), 6.90 (s, 1H), 6.42 (s, 1H), 6.35 (d, J=6.8, 1H), 5.08 (d, J=12.0, 1H), 4.98 (d, J=12.2, 1H), 4.20 (dd, J=12.9, 7.6, 1H), 3.84-3.95 (m, 2H), 3.83 (d, J=5.0, 2H), 2.42-2.19 (m, 2H), 2.07 (d, J=6.9, 1H), 1.96-1.83 (m, 1H), 1.39 (s, 9H). 13C NMR (101 MHz, DMSO) δ 171.79, 171.65, 170.82, 168.87, 163.04, 156.08, 136.86, 128.31, 127.74, 79.64, 65.58, 53.96, 42.17, 41.81, 31.25, 27.73, 27.01.

Source