Water → Ureidovaline

Participants

Reaction Conditions

Reaction Steps

To a stirred slurry of 95% NaH (560 mg, 23.2 mmol) at -10° C. in 20 mL of THF was slowly added N-methyl-N-((2-isopropyl-4-thiazolyl)methyl)amine (3.76 g, 22.1 mmol) keeping the temperature not more than 0° C. THF (5 mL) was added as a rinse. A solution of N-phenoxycarbonyl-L-Valine (5.0 g, 21.1 mmol) dissolved in 20 mL of THF was added slowly keeping the temperature not more than 0° C. THF (5 mL) was added as a rinse. After 4 hours, water (100 mL) was added, and the THF was removed under reduced pressure. The pH was adjusted to 9 with concentrated HCl, and the phenol by-product was removed with methyl tert-butyl ether washes (3×60 mL). The aqueous phase was stirred with 70 mL of toluene and adjusted to pH 3 with 4 N HCl. The aqueous phase was separated and extracted twice more with toluene (2×70 mL). The combined toluene extracts were concentrated under reduced pressure, and the residue was redissolved in toluene and heptane (50 mLs of a 1:1 v/v solution), warmed to 50° C. and allowed to cool to ambient temperature. The product was collected by filtration, washed with heptane and dried under vacuum to afford the title compound as a white powder in 83% yield.

Provenance & Evidence