Sodium hydride → Ureidovaline

Participants

Reaction Steps

To a stirred slurry of 60% oil dispersion NaH (200 mg, 5 mmol) at <5° C. in 10 mL of THF was added N-phenoxycarbonyl-L-Valine (1.0 g, 4.2 mmol) followed by a 10 mL THF rinse and keeping the temperature <5° C. using an ice-water bath. In another flask, N-methyl-N-((2-isopropyl-4-thiazolyl)methyl)amine (851 mg, 5 mmol) was added to a <5° C. slurry of 60% oil dispersion NaH (220 mg, 5.5 mmol) in 10 mL of THF maintaining the temperature <5° C. Both solutions were stirred for 15 minutes, and then the acid salt solution was added to the amine salt solution in one portion. The reaction was allowed to proceed at <10° C. for 1 hour and then at ambient temperature for 30 minutes. The reaction was quenched by the addition of 10 mL of MeOH, and the reaction mixture was then concentrated in vacuo. The resulting residue was dissolved in a minimum of EtOAc and flash chromatographed on silica gel eluting with 1:1 ethyl acetate in isopropanol. The residue obtained was further purified by preparative thin layer chromatography eluting with 33.6% CHCl3, 7.7% H2O, 3.5% HOAc, 25.2% MeOH and 30% EtOAc to afford the title compound (310 mg, 24%) as a yellow oil.

Provenance & Evidence