Trifluoroacetic acid → 1-(3-cyano-phenyl)-3-((R)-2-fluoro-4-morpholin-2-yl-phenyl)-urea

Temperature

80 °C

To a stirred solution of trifluoroacetic acid (216 μl) in water (4.5 ml) was added a solution of (R)-2-{4-[3-(3-cyano-phenyl)-ureido]-3-fluoro-phenyl}-morpholine-4-carboxylic acid tert-butyl ester (85 mg) in acetonitrile (2 ml). The reaction mixture was then capped and the mixture was shaken at 80° C. for 3 h. The reaction mixture was then cooled to room temperature and poured into 1 M aq. NaOH and the resulting mixture was extracted twice with EtOAc. The organic layers were dried over Na2SO4 and concentrated in vacuo. The crude material was purified by flash column chromatography (Isolute® Flash-NH2 from Separtis); gradient: heptane/EtOAc/MeOH) to afford 1-(3-cyano-phenyl)-3-((R)-2-fluoro-4-morpholin-2-yl-phenyl)-urea (45 mg, 61%) as a white solid. MS (ISP): 341.1 ([M+H]+).

1. customThe reaction mixture was then capped
2. temperatureThe reaction mixture was then cooled to room temperature
3. extractionthe resulting mixture was extracted twice with EtOAc
4. dry with materialThe organic layers were dried over Na2SO4
5. concentrationconcentrated in vacuo
6. customThe crude material was purified by flash column chromatography (Isolute® Flash-NH2 from Separtis)

ORD record

ord-a6a670f42a574e0996588f5cf3d3d3e1

Source dataset

uspto-grants-2015_05

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09029370B2