Diisopropylamine → 2-(2,4-Difluoroanilino)-4,5-difluorobenzoic acid

温度

-78 °C

Lithium diisopropylamide is generated at −5° C. by combining diisopropylamine (7.2 mL, 51 mmol) and n-butyllithium (33 mL, 53 mmol) in anhydrous tetrahydrofuran (150 mL) under an inert atmosphere. After 0.5 hour, the solution is cooled to −78° C. and 2,4-difluoroaniline (3.46 mL, 34 mmol) is added and stirred for 2 hours. 2,4,5-Trifluorobenzoic acid (3.0 g, 17 mmol) is added, and the mixture is subsequently allowed to warm to room temperature over 18 hours. A saturated solution of hydrogen chloride/dioxane (10 MIL) is added, and after 1 hour, the mixture is concentrated to a solid. The solid is dissolved in chloroform and washed with 1.0 M hydrochloric acid, water, and brine. The solution is dried, concentrated in vacuo, and purified by column chromatography (3:1 ethyl acetate/hexanes) to give 2-(2,4-difluoroanilino)-4,5-difluorobenzoic acid as a solid (2.18 g). 1H NMR (CDCl3): δ 8.95 (bs, 1H), 7.80–7.75 (m, 2H), 7.50–6.85 (m, 3H), 6.62–6.40 (m, 1H). MS EI: m/z 286 (M+).

1. customis generated at −5° C.
2. temperatureto warm to room temperature over 18 hours
3. waitafter 1 hour
4. concentrationthe mixture is concentrated to a solid
5. dissolutionThe solid is dissolved in chloroform
6. washwashed with 1.0 M hydrochloric acid, water, and brine
7. customThe solution is dried
8. concentrationconcentrated in vacuo
9. custompurified by column chromatography (3:1 ethyl acetate/hexanes)

ORDレコード

ord-0123970af20b4d508cbf2eed15a3b1af

出典データセット

uspto-grants-2006_08

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US07094780B1