N-Phenoxycarbonyl-L-valine → Ureidovaline

Participants

Reaction Conditions

Reaction Steps

To a suspension of LiOH monohydrate (1.06 g, 25.2 mmol) in THF (20 mL) at 0° C. to 5° C. was added 3.78 g (22.2 mmol) of N-methyl-N-((2-isopropyl-4-thiazolyl)methyl)amine, followed by a 5 mL THF rinse. To this solution was added a solution of N-phenoxycarbonyl-L-Valine (5.0 g, 21.1 mmol) in 20 mL of THF. Following a 5 mL THF rinse, 0.5 mL of water was added, and the reaction mixture was allowed to warm to 20° C. with stirring. After 6 hours, the reaction was cooled to 10° C. and quenched with water (55 mL). The THF was removed under reduced pressure, MTBE (50 mL) was added, and the biphasic solution was adjusted to pH 9.0 with 4 N HCl. The layers were separated and the aqueous layer was washed with an additional 50 mL of MTBE. The aqueous layer was sitrred with 130 mL of toluene and adjusted to pH 3 with 4 N HCl, and the phases were separated. The aqueous, product-containing layer was stirred with 50 mL of toluene and adjusted to pH=3.0 with 4N HCl. The aqueous layer was separated and extracted once more with 50 mL of toluene. The combined organic extracts were concentrated in vacuo. The residue obtained was redissolved in toluene, filtered and rinsed with toluene (approx. 50 mL total). The combined filtrates were concentrated in vacuo to an oil. Toluene (25 mL) and heptane (25 mL) were added and warmed to 50° C. The clear solution was allowed to cool until cloudy and then was seeded with N-((N-Methyl-N-((2-isopropyl-4-thiazolyl)methyl)amino)carbonyl)-L-Valine. The resulting slurry was stirred for at least 12 hours and the product was collected by filtration and washed with heptane (5 mL). The resulting solid was dried in a vacuum oven at 50° C. to yield the desired product as a white powder.

Provenance & Evidence