Benzoyl chloride → (1R,2S)-1-(3-chloro-4-cyano-2-methylphenylamino)-1-(5-phenyl-1,3,4-oxadiazol-2-yl)propan-2-yl benzoate

To a solution of 2-chloro-4-((1R,2S)-2-hydroxy-1-(5-phenyl-1,3,4-oxadiazol-2-yl)propylamino)-3-methylbenzonitrile (200 mg, 0.54 mmol) in pyridine (1.0 mL) and CH2Cl2 (7.0 mL) was added benzoyl chloride (94 μL, 0.81 mmol). Upon complete addition the reaction mixture was stirred for 60 h, then quenched with 10% aqueous HCl (15 mL). The mixture was partitioned between H2O (35 mL) and CH2Cl2 (40 mL). The aqueous layer was extracted with CH2Cl2 (35 mL). The combined organic extracts were washed with NaHCO3 (35 mL), dried (Na2SO4), filtered and concentrated under reduced pressure to provide an off white solid, which was purified by flash chromatography over silica gel (20-40% EtOAc in hexanes) to provide the title compound as a colourless solid (225 mg, 88%): 1H NMR (400 MHz, CDCl3, □ in ppm) 8.05 (dm, J=7.2 Hz, 2H), 7.91 (dm, J=7.2 Hz, 2H), 7.62 (tt, J=1.2, 7.4 Hz, 1H), 7.55-7.41 (m, 5H), 7.39 (d, J=8.6 Hz, 1H), 6.84 (d, J=8.8 Hz, 1H), 5.81 (pentet, J=6.3 Hz, 1H), 5.38 (d, J=7.6 Hz, 1H), 5.21 (dd, J=5.9, 7.4 Hz, 1H), 2.31 (s, 3H), 1.50 (d, J=6.5 Hz, 3H).

1. additionUpon complete addition the reaction mixture
2. customquenched with 10% aqueous HCl (15 mL)
3. customThe mixture was partitioned between H2O (35 mL) and CH2Cl2 (40 mL)
4. extractionThe aqueous layer was extracted with CH2Cl2 (35 mL)
5. washThe combined organic extracts were washed with NaHCO3 (35 mL)
6. dry with materialdried (Na2SO4)
7. filtrationfiltered
8. concentrationconcentrated under reduced pressure
9. customto provide an off white solid, which
10. customwas purified by flash chromatography over silica gel (20-40% EtOAc in hexanes)

ORD 기록

ord-966c0ff285d6403daf59d2d8e8fb99c2

출처 데이터셋

uspto-grants-2012_09

DOI

10.6084/m9.figshare.5104873.v1

특허 번호

US08268872B2