Formic Acid → N5-(tert-Butoxycarbonyl)-N2-[(4-{(2S)-2-[(tert-butoxycarbonyl)amino]-2-carboxyethyl}phenoxy)-carbonyl]-L-ornithyl-S-trityl-L-cysteinamide

Participants

Reaction Steps

5.27 g (5.65 mmol) of the compound from example 12A was dissolved in approx. 60 ml tetrahydrofuran. 2.1 ml (15.2 mmol) Triethylamine, 0.57 ml (15.2 mmol) formic acid and 0.35 g (0.30 mmol) tetrakis(triphenylphosphin)palladium(0) were added. The reaction mixture was stirred over night at room temperature. The reaction was diluted with approx. 60 ml water and twice extracted with approx. 50 ml dichloromethane. The combined organic phases were extracted with brine, dried over sodium sulfate and concentrated to dryness under reduced pressure. The raw product was dissolved in dichloromethane and chromatographed over approx. 500 ml silica gel. Solvents used were dichloromethane, dichloromethane/methanol 20/1 and dichloromethane/methanol 1/1. The product-containing fractions were combined and concentrated to dryness under reduced pressure. The raw product was further purified by preparative RP-HPLC on a C18 column with a water/methanol gradient to yield 1.37 g (24% of theory) product.

Provenance & Evidence