Water → HCID 59302360, compound

Participants

Reaction Steps

3-tert-Butyl-D-alanyl-3-tert-butyl-L-alanine (3.73 g, 12.1 mmol, example 92A) is dissolved in THF (170 ml) under an argon protective gas atmosphere. After the addition of water (170 ml), benzyloxycarbonyloxysuccinimide ester (4.52 g, 18.1 mmol, 1.5 equivalents) and N-methylmorpholine (4.28 g, 4.23 mmol, 3.5 equivalents) at 0° C., the mixture is stirred vigorously at RT until all starting material has been converted (several hours, HPLC monitoring, Method 2). The mixture is quenched with glacial acetic acid. The THF is drawn off in vacuo. The remaining aqueous phase is layered with ethyl acetate, adjusted to pH<3 with 4 N hydrochloric acid and then extracted several times with ethyl acetate. The organic phases are washed with brine, dried over sodium sulfate, filtered and concentrated. The resulting foam is stirred with acetonitrile, whereby a solid forms which is collected by filtration, then washed with a little acetonitrile. This process can be repeated several times more with the filtrate once it has been concentrated. The combined solids are dried under high vacuum whereby the title compound is obtained as a solid. The remaining mother liquor is concentrated and purified by means of preparative HPLC (Method 10). The title compound (combined solids and purification product from HPLC separation) is obtained as a solid (3.49 g, 71% of theory).

Provenance & Evidence