反应详情

温度

0 °C

A solution of 2-(4-fluoro-benzenesulfonyl)-benzene-1,4-diol (10.0 g, 37.3 mmol) in dry 1-methyl-2-pyrrolidinone (100 mL) with 3 Å molecular sieves (3.0 g) was sparged with dry nitrogen for 15 min at RT. The solution was cooled to 0° C. and potassium bis(trimethylsilyl)amide (18.59 g, 93.2 mmol) was added in a single portion to give a deep red suspension. The suspension was warmed to RT with continued sparging. 18-Crown-6 (10.8 g, 41.0 mmol) was added in a single portion and the solution was cooled to 0° C. To the cooled suspension was added 2-chloro-1,3-dimethyl-5-nitro-benzene (8.30 g, 44.7 mmol) to give a brown solution and sparging was ceased. The solution warmed to RT and stirred under dry nitrogen for 3 h. The crude reaction mixture was poured into 1M HCl (1 L) at 0° C. and extracted with EtOAc (3×300 mL). Combined extracts were washed with 1 M HCl (4×1 L) and brine (1 L), dried over anhydrous sodium sulfate, treated with activated carbon and filtered. The filtrate was concentrated to a tan solid which was filtered through silica gel (150 g) with 1:9:10 methanol:hexanes:CH2Cl2 (1.5 L). Concentration of the filtrate gave the title compound of Step C as a tan solid (11.4 g). The title product of Step C was used in the next step without further purification. MS (APCI−) Calc.: 417.1, Found: 416.0 (M−1).

1. customto give a deep red suspension
2. temperatureThe suspension was warmed to RT with continued sparging
3. temperaturethe solution was cooled to 0° C
4. customto give a brown solution
5. customsparging
6. temperatureThe solution warmed to RT
7. customThe crude reaction mixture
8. extractionextracted with EtOAc (3×300 mL)
9. washCombined extracts were washed with 1 M HCl (4×1 L) and brine (1 L)
10. dry with materialdried over anhydrous sodium sulfate
11. additiontreated with activated carbon
12. filtrationfiltered
13. concentrationThe filtrate was concentrated to a tan solid which
14. filtrationwas filtered through silica gel (150 g) with 1:9:10 methanol