反应详情

温度

130 °C

N,N-Dimethylformamide dimethylacetal (16.5 mL, 125 mmol) was added in one portion to a stirred solution of 4-fluoro-3-iodo-6-methylnitrobenzene (14.1 g, 50 mmol) in N,N-dimethylformamide (50 mL) at 130° C. under Ar. The mixture was stirred at 130° C. for 10 min then another aliquot of N,N-dimethylformamide dimethylacetal (10 mL) was added in one portion. The mixture was stirred at 130° C. for a further 10 min then another aliquot of N,-dimethylformamide (6 mL) was added in one portion. The mixture was stirred at 130° C. for 10 min then poured into water (400 mL) and extracted with ethyl acetate (3×150 mL). The combined organic extracts were washed with water (200 mL) and brine (200 mL) then dried (magnesium sulfate), filtered and concentrated in vacuo to leave a solid. The solid was dissolved in acetic acid, ethanol (1:1; 240 mL) and iron powder (33.2 g, 600 mmol) was added in one portion. The mixture was placed under an atmosphere of Ar, heated to 90° C. and stirred for 15 min (CARE: VIGOROUS REACTION—COOLING MAY BE REQUIRED). After cooling to room temperature the mixture was filtered through celite and the filtrate was concentrated in vacuo to leave a crude oil. The oil was purified by column chromatography [SiO2; dichloromethane, heptane (1:4 to 2:3)] to give the product (4.8 g, 37%, 3 steps from 2-fluoro-4-methyl-5-nitroaniline) as a green oil: NMR δH (400 MHz; CDCl3) 8.18 (1H, br. s), 7.75 (1H, d, J 5 Hz), 7.32 (1H, d, J 8.5 Hz), 7.22-7.23 (1H, m), 6.50-6.52 (1H, m); GC (25 m Quartz/Bonded Phase I; Injection Temperature 250° C.; Detector Temperature 320° C.; Temperature Ramp Rate: 100 to 320° C. at 10° C./min; Carrier Gas Helium; Flow Rate 12 mL/min) Retention Time: 8.65 min.

1. stirringThe mixture was stirred at 130° C. for a further 10 min
2. stirringThe mixture was stirred at 130° C. for 10 min
3. extractionextracted with ethyl acetate (3×150 mL)
4. washThe combined organic extracts were washed with water (200 mL) and brine (200 mL)
5. dry with materialthen dried (magnesium sulfate)
6. filtrationfiltered
7. concentrationconcentrated in vacuo
8. customto leave a solid
9. temperatureheated to 90° C.
10. stirringstirred for 15 min (CARE: VIGOROUS REACTION—COOLING MAY BE REQUIRED)
11. temperatureAfter cooling to room temperature the mixture
12. filtrationwas filtered through celite
13. concentrationthe filtrate was concentrated in vacuo
14. customto leave a crude oil
15. customThe oil was purified by column chromatography [SiO2; dichloromethane, heptane (1:4 to 2:3)]