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GPR40激动剂的合成 被引量：1

Synthesis of GPR40 Agonist 2-[6-[2',6'-Dimethyl-4'-[3-( methylsulfonyl) propoxy]biphenyl-3-ylmethoxy]-2,3-dihydro-1-benzofuran-yl]acetic Acid
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摘要 以3-甲硫基丙醇(2)与对甲基苯磺酰氯(3)发生取代反应、氧化反应得3-(甲基磺酰基)丙基-4-甲基苯磺酸(5),再以间苯二酚(6)与4-氯乙酰乙酸乙酯(7)缩合成环、水解、成酯、氢化还原得6-羟基-苯并呋喃-3-乙酸甲酯(11),以4-溴-3,5-二甲基苯酚(12)与3-甲酰基苯硼酸(13)发生suzuki偶联得4'-羟基-2',6'-二甲基-[1,1'-联苯]-3-甲醛(14),再与(4)亲核取代、还原得3-(甲基磺酰基)丙基-4-甲基苯磺酸(16),(16)与(11)缩合,最终水解得到6-({2',6'-二甲基-4'-[3-(甲磺酰基)丙酰基]-联苯}甲氧基)-2,3-二氢苯并呋喃-3-乙酸(18)。 3-（ methylthio） propan- 1- ol（ 2） was subjected to substitution with 4- methylbenzene- 1- sulfonyl chloride（ 3）,and then oxidation to 3-（ methylsulfonyl） propyl- 4- methylbenzensulfonate（ 5）,resorcinol（ 6） was condensed with ethyl- 4- chloro- 3-oxobutanoate（ 7）,which followed byhydrol- yzed,esterified,hydrogenated to afford methyl- 2-（ 6- hydroxy- 2,3- dihydrobenzofuran- 3- yl） acetate（ 11）. 4- bromo- 3,5- dimethylphenol（ 12） subjected to suzuki reaction with 3- formylphenyl- boronic acid（ 13） to get 4＇-hydroxy- 2＇,6＇- dimethylbiphenyl- 3- carbaldehyde（ 14）,which was substitution reaction with 5 and then reduction with Na BH4 to give（ 2,6＇- dimethyl- 4-（ 3-（ methylsulfonyl） propoxy） biphenyl- 3- yl） methanol（ 16）,followed by condensed,hydrolyzed to obtained 2-[6-[2＇,6＇- Dimethyl- 4＇-[3-（ methylsulfonyl） propoxy]biphenyl- 3- ylmethoxy]- 2,3- dihydro- 1- benzofuran- yl] acetic acid（ 18）.
作者 陆咏斌 唐春雷 冯柏年
机构地区 江南大学药学院
出处 《广州化工》 CAS 2015年第3期51-53,共3页 GuangZhou Chemical Industry
基金 中央高校自主科研项目(JUSRP1039)
关键词 GPR40激动剂 TAK875 合成 工艺优化 GPR40 agonist TAK-875 synthesis process optimization
分类号 R914.5 [医药卫生—药物化学]
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参考文献8

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二级参考文献46

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共引文献4

同被引文献27

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广州化工
2015年 第3期

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