反应 #1885100

反应方程式

1-chloro-4-fluoro-2-methoxy-3-methylbenzene

sodium amide

benzylamine

→

N-benzyl-3-fluoro-5-methoxy-4-methylaniline

收率 34.0%

溶剂

THF

反应条件

后处理

1. 1
   其他The reaction was quenched
2. 2
   温度by cooling in an ice bath
3. 3
   workup.ADDITIONfollowed by dropwise addition of saturated NH4Cl and water
4. 4
   workup.STIRRINGAfter stirring for 1 hour
5. 5
   workup.ADDITIONthe reaction mix
6. 6
   萃取was extracted twice with ethyl acetate
7. 7
   干燥the combined organic phases dried over MgSO4
8. 8
   浓缩concentrated via rotary evaporation
9. 9
   其他The crude product was purified by silica gel chromatography (0-30% ethyl acetate/hexanes)

实验过程

To a −78° C. cooled solution of 1-chloro-4-fluoro-2-methoxy-3-methylbenzene (470 mg, 2.69 mmol) in THF (5.5 mL) was added sodium amide (95%, 276 mg, 6.72 mmol). After 30 minutes, the solution was warmed to −20 to −30° C. and then benzylamine (441 μL, 4.05 mmol) was added dropwise over 1 minute. The reaction was stirred overnight, and LCMS showed no starting material. The reaction was quenched by cooling in an ice bath followed by dropwise addition of saturated NH4Cl and water. After stirring for 1 hour, the reaction mix was extracted twice with ethyl acetate, and the combined organic phases dried over MgSO4 and concentrated via rotary evaporation. The crude product was purified by silica gel chromatography (0-30% ethyl acetate/hexanes) to yield a 223 mg (34%) of N-benzyl-3-fluoro-5-methoxy-4-methylaniline as an orange oil. 1H NMR (300 MHz, CDCl3) δ 7.40-7.27 (m, 5H), 6.06-6.00 (m, 1H), 6.00 (s, 1H), 4.29 (s, 2H), 3.74 (s, 3H), 2.00 (s, 3H); LCMS (m/z): 246 (MH+).

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