Triethylamine → N-[2-bromo-6-chloro-4-(1,2,2,3,3,3-hexafluoro-1-trifluoromethylpropyl)phenyl]-4-cyano-3-nitrobenzamide

温度

90 °C

To a suspension of 2-bromo-6-chloro-4-(1,2,2,3,3,3-hexafluoro-1-trifluoromethyl-propyl)phenylamine (Example 3.3) (70 g, 165 mmol) in 1,2-dichloroethane (660 ml) was added triethylamine (50.09 g, 495 mmol), followed by 4-cyano-3-nitrobenzoic acid (made as in WO 2008/074427) (63.4 g, 330 mmol) and bis(2-oxo-3-oxazolidinyl)phosphonic chloride (“BOP-Cl”) (84 g, 330 mmol). The reaction mixture was stirred at 90° C. for 6 hours. The reaction was quenched by addition of aqueous hydrochloric acid (1M) (500 ml) and the phases were separated. The organic phase was washed with saturated aqueous sodium hydrogen carbonate and brine. The aqueous phase was extracted twice with 1,2-dichloroethane. The combined organic extracts were dried over sodium sulfate and concentrated. The residue was purified by column chromatography on silica gel (eluent: cyclohexane/ethyl acetate 7:3) to give N-[2-bromo-6-chloro-4-(1,2,2,3,3,3-hexafluoro-1-trifluoromethylpropyl)phenyl]-4-cyano-3-nitrobenzamide (89 g, 90% yield). 1H NMR (400 MHz, CDCl3): 8.89 (s, 1H), 8.40 (d, 1H), 8.12 (d, 1H), 7.88 (m, 2H), 7.72 (s, 1H).

1. customThe reaction was quenched by addition of aqueous hydrochloric acid (1M) (500 ml)
2. customthe phases were separated
3. washThe organic phase was washed with saturated aqueous sodium hydrogen carbonate and brine
4. extractionThe aqueous phase was extracted twice with 1,2-dichloroethane
5. dry with materialThe combined organic extracts were dried over sodium sulfate
6. concentrationconcentrated
7. customThe residue was purified by column chromatography on silica gel (eluent: cyclohexane/ethyl acetate 7:3)

ORDレコード

ord-84550790dbae4db984330ee02c76310e

出典データセット

uspto-grants-2013_04

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US08431514B2