反应详情

A solution of methyl 4-chloro-3′-fluoro-6-nitro-5-[(trimethylsilyl)ethynyl]biphenyl-2-carboxylate (330 g, 780 mmol) in ethyl acetate (1 L) was treated with methanol (1 L) and saturated aqueous ammonium chloride solution (670 mL, 10 mol). The mixture was cooled with an ice-water bath and treated with <10 micron zinc dust (310 g, 4.7 mol) in portions with internal temperature at 15 to 45° C. After addition, the ice bath was removed and the reaction mixture was stirred for 3 hours. The reaction mixture was filtered over a pad of celite and rinsed with ethyl acetate (2×1 L). The combined filtrate was diluted with brine (500 mL) and stirred for 10 minutes. The brine layer was separated and extracted with ethyl acetate (300 mL). The combined organic layers were dried over sodium sulfate, filtered, and concentrated to give a green oil which contained approximately 12% water. This material was dried with azeotropic drying with toluene to give the desired product (300 g, quantitative) as a green semi-solid. HPLC 90.5% pure @ 220 nm. LCMS for C19H20ClFNO2Si (M+H)+: m/z=376.1; Found: 376.0; 1H NMR (300 MHz, DMSO-d6): δ 7.56-7.42 (m, 1H), 7.28-7.16 (m, 7.28-7.16 (m, 1 H), 7.07 (s, 1 H), 7.06-6.94 (m, 2 H), 5.06 (s, 2 H), 3.47 (s, 3 H), 0.25 (s, 9 H).

1. temperatureThe mixture was cooled with an ice-water bath
2. additionAfter addition
3. customthe ice bath was removed
4. filtrationThe reaction mixture was filtered over a pad of celite
5. washrinsed with ethyl acetate (2×1 L)
6. additionThe combined filtrate was diluted with brine (500 mL)
7. stirringstirred for 10 minutes
8. customThe brine layer was separated
9. extractionextracted with ethyl acetate (300 mL)
10. dry with materialThe combined organic layers were dried over sodium sulfate
11. filtrationfiltered
12. concentrationconcentrated
13. customto give a green oil which
14. customThis material was dried
15. dry with materialwith azeotropic drying with toluene