Triethylamine → HCID 15291044, compound

Participants

Reaction Conditions

Reaction Steps

17.84 kg (70.88 mol) of Z-valine and 4.59 kg (74.42 mol) of triethylamine were dissolved in 170 l of methylene chloride in a 400 l vessel. To this solution were added at -5° to -10° C. 8.58 kg (70.88 mol) of pivaloyl chloride. After a reaction time of 2 h at -5° C., a solution of 24.2 kg of Val-MeVal-Pro-OMe in 86 l of methylene chloride was run in at -5° C. After a further 2 h at -5° C., the mixture was heated to 20° C. and stirred at this temperature for 12 h. 50 l of water were added for working up. After removal of the aqueous phase, the organic phase was extracted once with 40 l of 2N hydrochloric acid and twice with 40 l of 2N sodium hydroxide solution each time. The organic phase was washed until neutral and then the methylene chloride solvent was removed by distillation and replaced by 300 l of diisopropyl ether. The product was crystallized by heating the emulsion of the oily product to 60° C., adding seed crystals and keeping at 60° C. for 7 h. To complete the crystallization, the mixture was stirred further at 50° C. for 5 h and then at 40° C. for 5 h and subsequently cooled to 20° C. The suspension of crystals was discharged through a 120 l pressure filter.

Provenance & Evidence