Hydrochloric Acid → (4S,5R)-5-[3-fluoro-5-(trifluoromethyl)phenyl]-4-methyl-1,3-oxazolidin-2-one

Lithium tri-tert-butoxyaluminohydride (18.27 ml, 74.0 mmol) was added into a cold (dry ice/acetone bath) solution of benzyl {(2S)-1-[3-fluoro-5-(trifluoromethyl)phenyl]-1-oxopropan-2-yl}carbamate (5.4655 g, 14.80 mmol) in ethanol (100 ml). LCMS indicated the reaction was completed in 10 min. The reaction was quenched by HCl (1N). The crude mixture was diluted with ethyl acetate and filtered through a bed of Celite® 521 (slow filtration). Volatiles were removed from the filtrate under reduced pressure. The resulting pot residue was worked up with aqueous sodium hydrogen carbonate/brine, extracted with ethyl acetate, dried over Na2SO4, filtered and evaporated to afford a white solid. This solid was stirred with potassium hydroxide (10 ml, 75 mmol) in a THF (100 ml)/methanol (50 ml) mixture at room temp for 2 hrs. LCMS indicated completion of reaction. HCl (1N) was added to acidify the reaction mixture. Volatiles were removed under reduced pressure. The pot residue was worked up with brine, extracted with ethyl acetate, dried over Na2SO4, filtered and evaporated to afford a dark mixture. The resulting mixture was purified by flash chromatography (SiO2, Biotage 65i cartridge). The column was eluted by an ethyl acetate/hexanes mixture (0% to 100% ethyl acetate). Related fractions were pooled and evaporated under reduced pressure to afford a white solid of 2.6765 g as the titled compound. LCMS calc.=263.06. found=262.11 (M−1)−. 1H-NMR (CDCl3, 500 MHz) δ 7.36 (s, 1H), 7.34 (d, J=8.5 Hz, 1H), 7.27 (d, J=9 Hz, 1H), 5.8 (d, J=7.5 Hz, 2H), 4.3 (ps quintet, J=6.9 Hz, 1H), 0.85 (d, J=6.5 Hz, 3H).

1. customThe reaction was quenched by HCl (1N)
2. additionThe crude mixture was diluted with ethyl acetate
3. filtrationfiltered through a bed of Celite® 521 (slow filtration)
4. customVolatiles were removed from the filtrate under reduced pressure
5. extractionextracted with ethyl acetate
6. dry with materialdried over Na2SO4
7. filtrationfiltered
8. customevaporated
9. customto afford a white solid
10. customcompletion of reaction
11. customVolatiles were removed under reduced pressure
12. extractionextracted with ethyl acetate
13. dry with materialdried over Na2SO4
14. filtrationfiltered
15. customevaporated
16. customto afford a dark mixture
17. customThe resulting mixture was purified by flash chromatography (SiO2, Biotage 65i cartridge)
18. washThe column was eluted by an ethyl acetate/hexanes mixture (0% to 100% ethyl acetate)
19. customevaporated under reduced pressure

ORD-Eintrag

ord-97d5c0b16cf74d18aca1092c64b0b96b

Quelldatensatz

uspto-grants-2015_12

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US09221834B2