反应详情

温度

60 °C

Under argon atmosphere, a suspension of potassium tert-butanolate (71.6 g, 625 mmol) in DMSO (150 mL) was placed in a 1.5 L flask, fitted with a mechanical stirrer. Then diethyl malonate (97.9 mL, 625 mmol) was added drop wise at 20-30° C. under ice bath cooling. To the thick white suspension was the added solid commercially available 5-chloro-2-nitro-4-trifluoromethyl-phenylamine [CAS-No. 35375-74-7] (60.14 g, 250 mmol) in one portion, the mixture was diluted with DMSO (100 mL) and the red solution warmed up to 60° C. and stirred for 20 h at 60° C. The mixture was cooled to 23° C. and a solution of potassium hydroxide (85%, 65.24 g, 1 mol) in water (100 mL) was added drop wise. The mixture was then heated to 100° C. and stirred for further 4 h. The mixture was cooled to 23° C., diluted with water (ca. 1000 mL), acidified with 37% HCl 3 to pH 3, and extracted three times with tert-butyl methyl ether (TBME) The organic layers were washed with brine, dried over MgSO4 and evaporated to give a brown solid, which was triturated with hot heptane, filtered off and washed with heptane to give the title compound as a brown solid (50.0 g, 91%), which was used without further purification. MS (ISN) 218.9 [M−H].

1. customwas placed in a 1.5 L flask
2. customfitted with a mechanical stirrer
3. temperaturecooling
4. temperatureThe mixture was cooled to 23° C.
5. temperatureThe mixture was then heated to 100° C.
6. stirringstirred for further 4 h
7. temperatureThe mixture was cooled to 23° C.
8. extractionextracted three times with tert-butyl methyl ether (TBME) The organic layers
9. washwere washed with brine
10. dry with materialdried over MgSO4
11. customevaporated
12. customto give a brown solid, which
13. customwas triturated with hot heptane
14. filtrationfiltered off
15. washwashed with heptane