H-Dab(boc)-OH → (2S)-2-{[(4-{(2S)-3-(Allyloxy)-2-[(tert-butoxycarbonyl)amino]-3-oxopropyl}phenoxy)carbonyl]-amino}-4-[(tert-butoxycarbonyl)amino]butanoic acid

Participants

Reaction Conditions

Reaction Steps

7.50 g (15.4 mmol) of the compound from example 1A was dissolved in 150 ml dichloromethane. 3.36 g (15.4 mmol) (2S)-2-Amino-4-[(tert-butoxycarbonyl)amino]butanoic acid was added. The reaction mixture was split into 10 portions. The portions were heated for 30 min in a sealed tube at 75° C. in a microwave synthesizer. The combined reaction mixture was extracted with approx. 100 ml saturated ammonium chloride solution. The aqueous phase was twice back extracted with approx. 50 ml dichloromethane each. The combined organic phases were extracted with approx. 50 ml brine and dried over sodium sulfate. The solvent was removed under reduced pressure. The raw product was dissolved in dichloromethane and chromatographed over approx. 1 l silica gel. Solvents used were dicloromethane/ethyl acetate 4/1, dichloromethane/methanol 10/1 to dichloromethane/methanol 1/1. The product-containing fractions were combined and concentrated to dryness under reduced pressure. This gave 8.70 g (10.8 mmol, 70% of theory) of the desired product.

Provenance & Evidence