反应详情

A 5-L, four neck round bottom flask equipped with overhead stirrer, positive pressure nitrogen inlet, 500-mL addition funnel with nitrogen outlet and a thermocouple was charged with 2,6-dichloro-3-nitropyridin-4-amine (150.0 g, 0.72 mol) and MeOH (1.50 L) and the resulting brown suspension was stirred at room temperature. NaOCH3 (25% solution in MeOH, 260 mL, 1.155 mol) was charged to the addition funnel and added over 30 min (the temperature did not exceed 32° C.). The resulting red suspension was stirred for 1 h, then transferred to a 3-L round bottom flask (with MeOH) and evaporated to near dryness on a rotary evaporator. The resulting red sludge was diluted with aqueous ammonium chloride (1.75 L) and extracted with EtOAc (2×900 mL). The combined organics were washed with water (150 mL), the water layer was diluted with brine (100 mL) and back-extracted with EtOAc (100 mL). The combined organics were dried (MgSO4) and concentrated under reduced pressure at 60° C. to yield 6-chloro-2-methoxy-3-nitropyridin-4-amine as a yellow solid. 1H NMR (CHLOROFORM-d) δ: 6.36 (s, 1H), 6.14 (br. s., 2H), 4.04 (s, 3H)

1. additionadded over 30 min (the temperature
2. customdid not exceed 32° C.
3. stirringThe resulting red suspension was stirred for 1 h
4. customtransferred to a 3-L round bottom flask
5. custom(with MeOH) and evaporated
6. customon a rotary evaporator
7. additionThe resulting red sludge was diluted with aqueous ammonium chloride (1.75 L)
8. extractionextracted with EtOAc (2×900 mL)
9. washThe combined organics were washed with water (150 mL)
10. additionthe water layer was diluted with brine (100 mL)
11. extractionback-extracted with EtOAc (100 mL)
12. dry with materialThe combined organics were dried (MgSO4)
13. concentrationconcentrated under reduced pressure at 60° C.