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Nabilone, LY-109514, Cesamet

大麻隆Chemical Name: (?-trans-6,6-Dimethyl-3-(1,1-dimethylheptyl)-1-hydroxy-6,6a,7,8,10,10a-hexahydro-9H-dibenzo[b,d]pyran-9-one
CAS No. 51022-71-0
项目整合开发状态: Launched-1983
项目研究机构: Lilly (Originator), Valeant (Licensee)
合成路线:The condensation of diethyl 2-acetylglutarate (I) with 5-(1,1-dimethylheptyl)resorcinol (II) by means of POCl3 gives ethyl 7-(1,1-dimethylheptyl)-5-hydroxy-4-methyl-2-oxo-2H-1-benzopyran-3-propionate (III),which is cyclized by means of NaH in DMSO yielding 3-(1,1-dimethylheptyl)-7,10-dihydro-1-hydroxy-6H-dibenzo[b,d]pyran-6,9-(8H)-dione (IV).The ketalization of (IV) with ethylene glycol (A) and p-toluenesulfonic acid affords the ketal (V),which by a Grignard reaction with methylmagnesium iodide in refluxing ether is converted into dl-3-(1,1-dimethylheptyl)-6,6a,7,8-tetrahydro-1-hydroxy-6,6-dimethyl-9H-dibenzo[b,d]pyran-9-one (VI).Finally,this compound is reduced with Li in liquid ammonia.
📌 参考资料/链接:
参考文献标题:Nabilone
文献作者:Castar,J.; Weetman,D.F.
参考来源:Drugs Fut 1978,3(3),207

📄 详细内容


合成路线:The condensation of diethyl 2-acetylglutarate (I) with 5-(1,1-dimethylheptyl)resorcinol (II) by means of POCl3 gives ethyl 7-(1,1-dimethylheptyl)-5-hydroxy-4-methyl-2-oxo-2H-1-benzopyran-3-propionate (III),which is cyclized by means of NaH in DMSO yielding 3-(1,1-dimethylheptyl)-7,10-dihydro-1-hydroxy-6H-dibenzo[b,d]pyran-6,9-(8H)-dione (IV).The ketalization of (IV) with ethylene glycol (A) and p-toluenesulfonic acid affords the ketal (V),which by a Grignard reaction with methylmagnesium iodide in refluxing ether is converted into dl-3-(1,1-dimethylheptyl)-6,6a,7,8-tetrahydro-1-hydroxy-6,6-dimethyl-9H-dibenzo[b,d]pyran-9-one (VI).Finally,this compound is reduced with Li in liquid ammonia.

参考文献标题:Hexahydro-dibenzo[b,d]pyran-9-ones as analgesic drugs
文献作者:Archer,R.A.
参考来源:US 3944673


合成路线:The condensation of diethyl 2-acetylglutarate (I) with 5-(1,1-dimethylheptyl)resorcinol (II) by means of POCl3 gives ethyl 7-(1,1-dimethylheptyl)-5-hydroxy-4-methyl-2-oxo-2H-1-benzopyran-3-propionate (III),which is cyclized by means of NaH in DMSO yielding 3-(1,1-dimethylheptyl)-7,10-dihydro-1-hydroxy-6H-dibenzo[b,d]pyran-6,9-(8H)-dione (IV).The ketalization of (IV) with ethylene glycol (A) and p-toluenesulfonic acid affords the ketal (V),which by a Grignard reaction with methylmagnesium iodide in refluxing ether is converted into dl-3-(1,1-dimethylheptyl)-6,6a,7,8-tetrahydro-1-hydroxy-6,6-dimethyl-9H-dibenzo[b,d]pyran-9-one (VI).Finally,this compound is reduced with Li in liquid ammonia.

参考文献标题:Dihydroxyhexahydrodibenzo[b,d]pyrans
文献作者:Archer,R.A.
参考来源:DE 2451934; ES 431674; FR 2249664; GB 1487637; JP 50071678; US 3968125


合成路线:The condensation of diethyl 2-acetylglutarate (I) with 5-(1,1-dimethylheptyl)resorcinol (II) by means of POCl3 gives ethyl 7-(1,1-dimethylheptyl)-5-hydroxy-4-methyl-2-oxo-2H-1-benzopyran-3-propionate (III),which is cyclized by means of NaH in DMSO yielding 3-(1,1-dimethylheptyl)-7,10-dihydro-1-hydroxy-6H-dibenzo[b,d]pyran-6,9-(8H)-dione (IV).The ketalization of (IV) with ethylene glycol (A) and p-toluenesulfonic acid affords the ketal (V),which by a Grignard reaction with methylmagnesium iodide in refluxing ether is converted into dl-3-(1,1-dimethylheptyl)-6,6a,7,8-tetrahydro-1-hydroxy-6,6-dimethyl-9H-dibenzo[b,d]pyran-9-one (VI).Finally,this compound is reduced with Li in liquid ammonia.

参考文献标题:Hexahydro-dibenzo[b,d]pyran-9-ones as an anti-anxiety drug
文献作者:Archer,R.A.
参考来源:DE 2451932; ES 431675; FR 2249663; GB 1487636; JP 50082073; NL 7414437; US 3928598


合成路线:The condensation of diethyl 2-acetylglutarate (I) with 5-(1,1-dimethylheptyl)resorcinol (II) by means of POCl3 gives ethyl 7-(1,1-dimethylheptyl)-5-hydroxy-4-methyl-2-oxo-2H-1-benzopyran-3-propionate (III),which is cyclized by means of NaH in DMSO yielding 3-(1,1-dimethylheptyl)-7,10-dihydro-1-hydroxy-6H-dibenzo[b,d]pyran-6,9-(8H)-dione (IV).The ketalization of (IV) with ethylene glycol (A) and p-toluenesulfonic acid affords the ketal (V),which by a Grignard reaction with methylmagnesium iodide in refluxing ether is converted into dl-3-(1,1-dimethylheptyl)-6,6a,7,8-tetrahydro-1-hydroxy-6,6-dimethyl-9H-dibenzo[b,d]pyran-9-one (VI).Finally,this compound is reduced with Li in liquid ammonia.
参考文献标题:Hexahydro-dibenzo[b,d]pyran-9-ones as psychotropic,particularly anti-depressant drugs
文献作者:Archer,R.A.
参考来源:US 3953603


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