反应详情

温度

90 °C

tert-Butyl 2,6-dichloro-4,5-dimethylnicotinate (1.9 g, 6.9 mmol, 1 equiv), Pd2(dba)3 (0.63 g, 0.69 mmol, 0.1 equiv), xantphos (0.80 g, 1.38 mmol, 0.2 equiv), and Cs2CO3 (5.4 g, 16.5 mmol, 2.4 equiv) was slurried in dioxane (deoxygenated by bubbling nitrogen through it for 10 min) added. Benzophenone imine (1.4 mL, 8.3 mmol, 1.2 equiv) was added and the mixture was heated at 90° C. for 2 h. Upon cooling to ambient temperature, the reaction was diluted with EtOAc and washed with water, dried (Na2SO4), and concentrated in vacuo. The crude product was taken up in MeOH (80 mL) and NaOAc (1.69, 20.6 mmol, 3 equiv) and hydroxlamine hydrochloride (0.96 g, 13.8 mmol, 2 equiv) was added. After 18 h, the reaction was added to 1 N NaOH and extracted with DCM (×2). The combined DCM extracts were dried (Na2SO4) and concentrated in vacuo. The crude product was purified by flash column chromatography (0-100% EtOAc/hex) to afford the product (1.1 g, 62%) as a yellow solid. 1H NMR (400 MHz, CDCl3) δ 4.57 (br. s., 2H), 2.24 (s, 3H), 2.03 (s, 3H), 1.60 (s, 9H); LCMS (ESI, M+1): 257.15.

1. additionadded
2. temperatureUpon cooling to ambient temperature
3. washwashed with water
4. dry with materialdried (Na2SO4)
5. concentrationconcentrated in vacuo
6. extractionextracted with DCM (×2)
7. dry with materialThe combined DCM extracts were dried (Na2SO4)
8. concentrationconcentrated in vacuo
9. customThe crude product was purified by flash column chromatography (0-100% EtOAc/hex)