反应 #7819

反应方程式

N-(2-hydroxyphenyl)-3-methoxy-4-methylbenzamide

p-toluenesulfonic acid monohydrate

→

2-(3-methoxy-4-methylphenyl)-1,3-benzoxazole

溶剂

toluene

反应条件

后处理

1. 1
   温度was refluxed overnight
2. 2
   温度After cooling
3. 3
   其他reaction to rt
4. 4
   过滤filtered
5. 5
   洗涤washing
6. 6
   其他The resulting brown oil was purified by flash chromatography on silica gel using 1:4 EtOAc

实验过程

3-Methoxy-4-methyl benzoic acid (1.2 g, 7.2 mmol) and thionyl chloride (10 mL) was heated to reflux conditions under argon until no starting material was observed by TLC. After cooling mixture to rt and concentration in vacuo, the resulting brown oil was dissolved in THF (15 mL) and slowly added to a cooled mixture of 2-aminophenol (780 mg, 7.1 mmol), diisopropylethyl amine (1.5 mL, 8.6 mmol) and THF (20 mL) at 0° C. Reaction mixture was allowed to warm to rt. After one hour, no starting material acid was observed by TLC. After concentrating reaction mixture in vacuo, the resulting brown oil was purified by flash chromatography on silica gel, using 1:4 EtOAc:hexanes. This afforded the desired intermediate, N-(2-hydroxyphenyl)-3-methoxy-4-methylbenzamide, as a yellow solid. A mixture of N-(2-hydroxyphenyl)-3-methoxy-4-methylbenzamide (1.5 g, 5.88 mmol), toluene (30 mL), p-toluenesulfonic acid monohydrate (7.6 g, 40 mmol) and molecular sieves was refluxed overnight. After cooling reaction to rt, filtered washing with warn chloroform and concentrated filtrate in vacuo. The resulting brown oil was purified by flash chromatography on silica gel using 1:4 EtOAc:hexanes to give the desired intermediate, 2-(3-methoxy-4-methylphenyl)-1,3-benzoxazole, as a colorless solid.

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