methyl (S)-2-amino-3-(4-but-2-ynyloxy-phenyl)-propionate → tert-butyl (E)-(2S,3S)-3-[(S)-2-(4-but-2-ynyloxy-phenyl)-1-methoxycarbonyl-ethylcarbamoyl]-12,12-difluoro-2-hydroxy-2-(2-methoxy-ethyl)-nonadec-4-enoate

Participants

Reaction Conditions

Reaction Steps

tert-Butyl (E)-(2S,3S)-12,12-difluoro-2-hydroxy-3-((S)-4-isopropyl-2-oxo-5,5-diphenyl-thiazolidine-3-carbonyl)-2-(2-methoxy-ethyl)-nonadec-4-enoate (No. 5552816; 38.8 mg, 0.0494 mmol) synthesized in Steps B1 to B6 and methyl (S)-2-amino-3-(4-but-2-ynyloxy-phenyl)-propionate (18.3 mg, 0.074 mmol) were dissolved in dichloromethane, and the solvent was distilled off under reduced pressure. The obtained mixture was stirred at 45° C. for 4 days, cooled to room temperature, and then extracted by adding ethyl acetate and water. The organic layer was washed with a saturated brine, dried over anhydrous sodium sulfate, and then filtered. The solvent was distilled out of the filtrate under reduced pressure and the residue was purified with SP1 (SiO2 cartridge, 25% ethyl acetate/n-hexane, Rf=0.1) to obtain tert-butyl (E)-(2S,3S)-3-[(S)-2-(4-but-2-ynyloxy-phenyl)-1-methoxycarbonyl-ethylcarbamoyl]-12,12-difluoro-2-hydroxy-2-(2-methoxy-ethyl)-nonadec-4-enoate (No. 6804236; 28.9 mg, 80% yield).

Provenance & Evidence