Triethylamine → N-(4-Fluorophenyl)-N'-(2-fluoro-4-hydroxyphenyl)cyclopropane-1,1-dicarboxamide

To a solution of 1-(4-fluorophenylcarbamoyl)cyclopropanecarboxylic acid (1.02 g) in N,N-dimethylformamide (5.0 ml) were added triethylamine (1.28 ml) and benzotriazol-1-yloxytris(dimethylamino)phosphonium hexafluorophosphate (2.03 g), followed by stirring at room temperature for 5 min. To this was added 4-amino-3-fluorophenol hydrochloride (500 mg), followed by stirring at room temperature for 3 days. The reaction mixture was partitioned between ethyl acetate and a 1N aqueous solution of sodium hydroxide. The organic layer was washed with a 1N aqueous solution of sodium hydroxide. To the aqueous layer was added 5N hydrochloric acid to make it acidic, this was extracted with ethyl acetate. The organic layer was washed with brine and dried over anhydrous sodium sulfate. The solvent was removed and the residue was purified by silica gel column chromatography (eluent; heptane:ethyl acetate=2:3 to 1:2). Fractions containing the target compound were concentrated under reduced pressure to provide the titled compound as a pale red solid (395 mg, 39%).

1. stirringby stirring at room temperature for 3 days
2. customThe reaction mixture was partitioned between ethyl acetate
3. washThe organic layer was washed with a 1N aqueous solution of sodium hydroxide
4. additionTo the aqueous layer was added 5N hydrochloric acid
5. extractionthis was extracted with ethyl acetate
6. washThe organic layer was washed with brine
7. dry with materialdried over anhydrous sodium sulfate
8. customThe solvent was removed
9. customthe residue was purified by silica gel column chromatography (eluent; heptane:ethyl acetate=2:3 to 1:2)
10. additionFractions containing the target compound
11. concentrationwere concentrated under reduced pressure

ORD 기록

ord-f2d05b8f36634f6d93d7b70d97690af8

출처 데이터셋

uspto-grants-2012_10

DOI

10.6084/m9.figshare.5104873.v1

특허 번호

US08288538B2