Diisopropylethylamine → N-tert-butoxycarbonyl O-allyl L-seryl L-valyl L-valyl O-allyl L-seryl glycine methyl ester

Participants

Reaction Conditions

Reaction Steps

O-allyl L-seryl methyl ester trifluoroacetate 20 (7.03 g, 21.3 mmol), N-tert-butoxycarbonyl O-allyl L-seryl L-valyl L-valine 15 (9.45 g, 21.3 mmol) and N,N-diisopropylethyl amine (2.75 g, 21.3 mmol) were dissolved in CH2Cl2 (100 mL) and the solution cooled to 0° C. (icebath). HOBt hydrate (3.26 g, 21.3 mmol) and then EDC hydrochloride (4.49 g, 23.4 mmol) were added in small portions. The reaction mixture was stirred for 1 h 30 min at 0° C. after which the icebath was removed and the mixture stirred for 14 h 30 min. The volume was then increased by addition of CH2Cl2 (200 mL) and the mixture stirred for another 7 hours before the volume was increased to 400 mL. The suspension was washed with 2M aqueous H2SO4 (150+300+450 mL), 7.5% (w/w) aqueous K2CO3 (150+300+450 mL), saturated brine (400 mL) and water (400+600 mL). The suspension was then diluted with CH2Cl2 (1.5 L) and dried with 3 Å molecular sieves resulting in a slightly turbid solution.

Provenance & Evidence