Triethylamine → 1-[(4-Fluorophenyl)carbamoyl]cyclopropanecarboxylic Acid

Temperature

0 °C

The title compound was prepared based on a modified procedure of Shih and Rankin [Synthetic Communications, 1996, 26(4), 833-836]: To a mixture of cyclopropane-1,1-dicarboxylic acid (21.2 g, 0.163 mol, 1.0 eq.) in anhydrous THF (200 mL) under nitrogen was added dropwise triethylamine (16.49 g, 0.163 mol, 1.0 eq.) with stirring for 30 minutes at 0° C., followed by the addition of thionyl chloride (19.39 g, 0.163 mol, 1.0 eq.) with stirring for another 30 minutes at 0° C. To the resulting mixture under nitrogen was added dropwise a solution of 4-fluoroaniline (19.92 g, 0.179 mol, 1.1 eq.) in anhydrous THF (100 mL) with stirring for 1.5 hours at 0° C. The reaction mixture was diluted with ethyl acetate and washed with 1N NaOH. The layers were separated, and the ethyl acetate layer was concentrated in vacuo to give a brownish solid. The brownish solid was washed with small amount of cold ethyl acetate, filtered and dried under vacuum to yield 1-(4-fluoro-phenylcarbamoyl)-cyclopropanecarboxylic acid as a white solid (23.71 g, 65.18%). 1H NMR (400 MHz, CD3OD): 7.57-7.53 (m, 2H), 7.05-7.00 (m, 2H) 1.46-1.43 (m, 2H), 1.40-1.37 (m, 2H).

1. customThe title compound was prepared
2. stirringwith stirring for another 30 minutes at 0° C
3. stirringwith stirring for 1.5 hours at 0° C
4. washwashed with 1N NaOH
5. customThe layers were separated
6. concentrationthe ethyl acetate layer was concentrated in vacuo
7. customto give a brownish solid
8. washThe brownish solid was washed with small amount of cold ethyl acetate
9. filtrationfiltered
10. customdried under vacuum

ORD record

ord-e5651635a5724cc6bc442d42eb23853e

Source dataset

uspto-grants-2009_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07579473B2