Tetrahydrofuran → 3-(2-Chloro-4-nitro-benzoyl)-4-methoxy-benzoic acid methyl ester

温度

-50 °C

A dry flask was charged with 3-iodo-4-methoxy-benzoic acid methyl ester (8.9 g, 30.5 mmol) and the flask was evaporated and then filled with argon and this process repeated twice. Dry THF (50 mL) was added, and the solution cooled to −50° C.; then isopropylmagnesium chloride (15.2 mL, 2.0 M in diethyl ether, 30.5 mmol) was added slowly over 20 min keeping the temperature below −40° C. On completion of the addition the reaction mixture was stirred at −40° C. for 45 min. A THF solution of ZnCl2 (5.19 g, 38.1 mmol, 1.0 M) was added dropwise over 20 min. The reaction mixture was stirred at 0° C. for 20 min; then 2-chloro-4-nitro-benzoyl chloride (7.04 g, 32.0 mmol) and Cu(OAc)2 (122 mg, 0.61 mmol) were added and the reaction mixture was allowed to warm to room temperature. After 16 h the reaction mixture was poured into a mixture of EtOAc/water, then shaken and separated. The aqueous phase was extracted with more EtOAc. The organic phases were combined, dried (MgSO4), filtered, and concentrated in vacuo to afford the crude product. The crude product was purified by flash chromatography using EtOAc/petroleum ether (40-60) 1:6 followed by 1:3 as the eluent to give the title compound as yellow solid.

1. customthe flask was evaporated
2. additionfilled with argon
3. additionDry THF (50 mL) was added
4. customthe temperature below −40° C
5. additionOn completion of the addition the reaction mixture
6. stirringThe reaction mixture was stirred at 0° C. for 20 min
7. temperatureto warm to room temperature
8. stirringshaken
9. customseparated
10. extractionThe aqueous phase was extracted with more EtOAc
11. dry with materialdried (MgSO4)
12. filtrationfiltered
13. concentrationconcentrated in vacuo
14. customto afford the crude product
15. customThe crude product was purified by flash chromatography

ORDレコード

ord-cccbafb37eb34f29bb7a0b723d965910

出典データセット

uspto-grants-2011_07

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US07977387B2