Hydrochloric Acid → Ureidovaline

Participants

Reaction Steps

To a stirred slurry of 95% NaH (355 mg, 14.1 mmol) at -5° C. in 15 mL of THF was added a solution of N-phenoxycarbonyl-L-Valine (2.99 g, 12.6 mmol) and N-methyl-N-((2-isopropyl-4-thiazolyl)methyl)amine (2.16 g, 12.7 mmol) in 15 mL of THF followed by a 5 mL THF rinse. The reaction mixture was stirred at or below 0° C. for three hours and then allowed to warm to ambient temperature. After two days at ambient temperature, the THF was removed under reduced pressure. The remaining aqueous residue was added to 31 mL of methyl tert-butyl ether and treated with stirring with a solution of 0.15 mL (1.8 mmol) of concentrated hydrochloric acid in 30 mL of water. The pH of the solution was adjusted to ~9 with 10% sodium hydroxide solution. The aqueous phase was washed with 30 mL of methyl tert-butyl ether. The aqueous phase was treated with 30 mL of toluene and acidified to pH 3 with 4 N HCl. The aqueous layer was separated and extracted with an additional 30 mL aliquot of toluene. The combined toluene extracts were concentrated under reduced pressure. The title compound was crystallized from toluene-heptane as a crystalline solid (3.32 g, 84%). m.p. 82.8-93.8° C. 1H NMR (CDCl3, 400 MHz) δ 1.02 (d, 3H), 1.04 (d, 3H), 1.38 (d, 6H), 2.30 (m, 1H), 2.30 (m, 1H), 3.00 (s, 3H), 3.28 (m, 1H), 4.24 (dd, 1H), 4.48 (AB quartet, 2H), 6.10-6.14 (br s, 1H), 7.02 (s, 1H). 13C NMR (CDCl3, 400 MHz) δ 18.1, 19.5, 23.0, 23.1, 29.9, 33.1, 34.9, 49.2, 59.6, 114.4, 149.4, 151.5, 159.8, 174.9. IR (film) 3200-3400, 1730,1620 cm-1. High Resolution MS Calc for C14H23N3SO3 : (FAB) m/e 314.1538 (M+H)+. Found: 314.1530.

Provenance & Evidence