Citric Acid → 3-chloro-5-({2-chloro-5-[(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)methyl]phenyl}oxy)benzonitrile

2-[(4-Chloro-3-hydroxyphenyl)methyl]-1H-isoindole-1,3(2H)-dione (0.50 g, 2.3 mmol), 3-chloro-5-fluorobenzonitrile (0.54 g, 3.5 mmol), K2CO3 (1.0 g, 7.0 mmol) and NMP (5.0 mL) were added to a round bottom flask. The reaction mixture was placed in an oil bath at 110° C. and stirred overnight. The reaction mixture was cooled to RT and aqueous 10% citric acid (25 mL) and EtOAc (25 mL) were added. Additional aqueous 10% citric acid was added until pH ˜4-5, the layers were separated and the aqueous layer was extracted with EtOAc (2×25 mL). The organic extracts were combined, dried over Na2SO4, filtered and evaporated. Purification was accomplished by column chromatography (hexane/EtOAc) to afford the title compound (0.47 g, 81%) as a solid. 1H NMR (400 MHz, DMSO-d6): δ ppm 7.81-7.92 (m, 4H), 7.79 (d, 1H), 7.58 (d, 1H), 7.44 (d, 1H), 7.37 (d, 1H), 7.29 (d, 1H), 7.23 (dd, 1H), 4.77 (s, 2H). MS: m/z 444.9 (M+23).

1. customThe reaction mixture was placed in an oil bath at 110° C.
2. customthe layers were separated
3. extractionthe aqueous layer was extracted with EtOAc (2×25 mL)
4. dry with materialdried over Na2SO4
5. filtrationfiltered
6. customevaporated
7. customPurification

ORD-Eintrag

ord-39aa689bc2034003902ea1e56d746a9d

Quelldatensatz

uspto-grants-2012_11

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US08304419B2