Lithium hydroxide, monohydrate → Ureidovaline

Participants

Reaction Steps

To lithium hydroxide monohydrate (1.06 g, 25.2 mmol) slurried in 20 mL of THF and cooled to less than 5° C. in an ice bath was added N-methyl-N-((2-isopropyl-4-thiazolyl)methyl)amine (3.78 g, 22.2 mmol) followed by a 5 mL THF rinse. A solution of N-phenoxycarbonyl-L-Valine (5.0 g, 21.1 mmol) in 20 mL of THF was added followed by a 5 mL THF rinse. Water (1.04 mL) was added, the cooling bath was removed, and the reaction was stirred at ambient temperature for 4.5 hours. Water (55 mL) was added, and the THF was removed under reduced pressure. Methyl tert-butyl ether (50 mL) was added, and as the solution stirred, the pH was adjusted to 9 with 4 N HCl. The aqueous phase was separated and washed with another 50 mL portion of MTBE. The aqueous product layer was stirred with 50 mL of toluene and adjusted to pH 3 with 4 N HCl. The aqueous layer was separated and extracted once more with toluene (50 mL). The combined toluene extracts were concentrated under reduced pressure. The residue obtained was redissolved in toluene, filtered, and rinsed with toluene. The combined filtrates were concentrated under reduced pressure. The product was crystallized from toluene-heptane (50 mLs of a 1:1 v/v solution), washed with heptane, and dried under vacuum to afford the title compound as a white powder.

Provenance & Evidence