反应 #1763515

反应方程式

Iodomethane

5-bromo-2-chloropyrimidin-4(3H)-one

DMF

LiH

→

desired product

收率 72.0%

5-bromo-2-chloro-3-methylpyrimidin-4(3H) -one

收率 72.0%

溶剂

DME

反应条件

后处理

1. 1
   workup.STIRRINGthe reaction mixture was stirred at room temperature for 30 minutes
2. 2
   workup.WAITat 60° C. for 1.5 hours
3. 3
   其他The reaction mixture was quenched with H2O
4. 4
   其他partitioned between EtOAc and saturated aqueous NaCl
5. 5
   其他The phases were separated
6. 6
   萃取the aqueous phase was re-extracted with EtOAc (1×)
7. 7
   干燥The combined organic layers were dried (Na2SO4)
8. 8
   过滤filtered
9. 9
   浓缩concentrated
10. 10
    其他to yield a crude yellow oil
11. 11
    其他The crude product was purified by flash column chromatography
12. 12
    洗涤eluting with 25:1 dichloromethane/EtOAc

实验过程

To a solution of 5-bromo-2-chloropyrimidin-4(3H)-one (1.00 g, 4.78 mmol) in DME (12 mL)/DMF (3 mL) under nitrogen at 0° C., LiH (0.044 g, 5.25 mmol) was added, and the reaction mixture was stirred for 15 minutes at room temperature. Iodomethane (0.589 mL, 9.45 mmol) was then added and the reaction mixture was stirred at room temperature for 30 minutes and then at 60° C. for 1.5 hours. The reaction mixture was quenched with H2O and then partitioned between EtOAc and saturated aqueous NaCl. The phases were separated, and the aqueous phase was re-extracted with EtOAc (1×). The combined organic layers were dried (Na2SO4), filtered and concentrated to yield a crude yellow oil. The crude product was purified by flash column chromatography, eluting with 25:1 dichloromethane/EtOAc. The desired product (0.764 g, 72%) was obtained as a yellow crystalline solid. 1H NMR (400 MHz, DMSO-d6) δ 8.26 (s, 1H), 3.59 (s, 3H). LRMS (ESI pos) m/e 223, 225 (M+, Br pattern).

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