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

온도

45 °C

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).

1. distillationthe solvent was distilled off under reduced pressure
2. temperaturecooled to room temperature
3. extractionextracted
4. additionby adding ethyl acetate and water
5. washThe organic layer was washed with a saturated brine
6. dry with materialdried over anhydrous sodium sulfate
7. filtrationfiltered
8. distillationThe solvent was distilled out of the filtrate under reduced pressure
9. customthe residue was purified with SP1 (SiO2 cartridge, 25% ethyl acetate/n-hexane, Rf=0.1)

ORD 기록

ord-a0e14b1483cc4692a045a1c5234a742c

출처 데이터셋

uspto-grants-2016_02

DOI

10.6084/m9.figshare.5104873.v1

특허 번호

US09266853B2