Heptane → Ureidovaline

Participants

Reaction Conditions

Reaction Steps

To a suspension of LiOH monohydrate (3.2 kg, 76.54 mol) in THF (66 kg) at 0° C. to 6° C. was added 11.3 kg (66.4 mol) of N-methyl-N-((2-isopropyl-4-thiazolyl)methyl)amine, followed by a 15 kg THF rinse. To this solution was added a cooled (0° C. to 6° C.) solution of N-phenoxycarbonyl-L-Valine (15 kg, 63.22 mol) dissolved in 41 kg of THF. Following a 25 kg THF rinse, 3.5 kg of water was added, and the reaction mixture was allowed to warm to 20° C. After 3 hours, the reaction was cooled to 10° C. and quenched with water (180 kg). The THF was removed under reduced pressure, MTBE (111 kg) 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 111 kg of MTBE. The aqueous layer was stirred with 130 kg of toluene and adjusted to pH 3 with 4 N HCl, and the phases were separated. The aqueous layer was back-extracted once more with 130 kg of toluene. The combined organic extracts were filtered and the material removed by filtration washed with toluene (50 kg). The combined filtrates were concentrated in vacuo. The residue obtained was redissolved in 100 kg of toluene and re-concentrated in vacuo. The residue obtained was cystallized using toluene and heptane to afford 16.6 kg (83.8%) of the title compound.

Provenance & Evidence