Water → Ureidovaline

Participants

Reaction Conditions

Reaction Steps

To a solution of LiOH monohydrate (970 mg, 23.2 mmol) and phenol (2.18 g, 23.2 mmol) dissolved in 25 mL of THF and cooled with an ice bath to 3-6° C. was added N-methyl-N-((2-isopropyl-4-thiazolyl)methyl)amine (3.95 g, 23.2 mmol) followed by a 1 mL THF rinse. To this mixture was slowly added a solution of N-phenoxycarbonyl-L-Valine (5.0 g, 21.1 mmol) dissolved in 20 mL of THF maintaining the temperature between 3° C. and 8° C. Following the addition and a 5 mL THF rinse, the cooling bath was removed, and the reaction was allowed to warm to ambient temperature. After stirring for 3 hours at ambient temperature, an additional aliquot of LiOH monohydrate (440 mg, 10.4 mmol) was added. One hour later, the reaction was treated with 100 mL of water and the THF removed under reduced pressure. The aqueous phase was adjusted to pH 9 using concentrated HCl and then washed with MTBE (3×60 mL). Toluene (60 mL) was added to the aqueous phase which was then acidified to pH 2.5 using 4 N HCl. The toluene phase was separated, and the aqueous phase was back extracted with four 60 mL aliquots of toluene. The combined organic extracts were concentrated under reduced pressure. The oil obtained was crystallized from toluene-heptane to give the title compound (5.41 g, 82%).

Provenance & Evidence