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Motretinide, Ro-11-1430, Tasmaderm

毛替垂尼Chemical Name: all-trans-N-Ethyl-9-(4-methoxy-2,3,6-trimethylphenyl)-3,7-dimethyl-2,4,6,8-nonatetraenamide
CAS No. 56281-36-8
项目整合开发状态: Launched-1980
项目研究机构: Roche (Originator), Gebro Pharma (Licensee)
合成路线:The methylation of 2,3,5-trimethylphenol (I) with MeI and KOH in 10% aqueous ethanol gives 2,3,5-trimethylanisole (II),which is formylated with DMF and POCl3 yielding 2,3,6-trimethyl-p-anisylaldehyde (III).The condensation of (III) with acetone (B) by means of NaOH affords 4-(4-methoxy-2,3,6-trimethylphenyl)but-3-en-2-one (IV),which by a Grignard reaction with ethynylmagnesium bromide (C) in THF is converted into the acetylenic alcohol (V).Partial hydrogenation of (V) with H2 over Pd/C in hexane gives dienic alcohol (VI),which is condensed with triphenylphosphine hydrobromide in benzene affording 5-(4-methoxy-2,3,6 trimethylphenyl)-3-methylpenta-2,4-diene-1-triphenylphosphonium bromide (VII).A Wittig condensation of (VII) with butyl 3-formylcrotonate (VIII) by means of NaH in DMF gives butyl 9-(4-methoxy-2,3,6-trimethylphenyl)-3,7-dimethylnona-2,4,6,8-tetraenoate (IX),which is hydrolyzed with KOH in refluxing ethanol-water yielding the corresponding free acid (X).This acid is converted into the acyl chloride (XI) by treatment with PCl3 in refluxing benzene.Finally,this compound is treated with ethylamine (E) in ether.The butyl 3-formylcrotonate (VIII) is obtained as follows: The oxidation of dibutyl tartrate (XII) with lead tetraacetate in benzene gives butyl glyoxalate (XIII),which is then condensed with propionaldehyde (XIV) by heating at 110 C with dibutyl-amine (D).
📌 参考资料/链接:
参考文献标题:Motretinide
文献作者:Castar,J.; Hillier,K.
参考来源:Drugs Fut 1978,3(2),126

📄 详细内容


合成路线:The methylation of 2,3,5-trimethylphenol (I) with MeI and KOH in 10% aqueous ethanol gives 2,3,5-trimethylanisole (II),which is formylated with DMF and POCl3 yielding 2,3,6-trimethyl-p-anisylaldehyde (III).The condensation of (III) with acetone (B) by means of NaOH affords 4-(4-methoxy-2,3,6-trimethylphenyl)but-3-en-2-one (IV),which by a Grignard reaction with ethynylmagnesium bromide (C) in THF is converted into the acetylenic alcohol (V).Partial hydrogenation of (V) with H2 over Pd/C in hexane gives dienic alcohol (VI),which is condensed with triphenylphosphine hydrobromide in benzene affording 5-(4-methoxy-2,3,6 trimethylphenyl)-3-methylpenta-2,4-diene-1-triphenylphosphonium bromide (VII).A Wittig condensation of (VII) with butyl 3-formylcrotonate (VIII) by means of NaH in DMF gives butyl 9-(4-methoxy-2,3,6-trimethylphenyl)-3,7-dimethylnona-2,4,6,8-tetraenoate (IX),which is hydrolyzed with KOH in refluxing ethanol-water yielding the corresponding free acid (X).This acid is converted into the acyl chloride (XI) by treatment with PCl3 in refluxing benzene.Finally,this compound is treated with ethylamine (E) in ether.The butyl 3-formylcrotonate (VIII) is obtained as follows: The oxidation of dibutyl tartrate (XII) with lead tetraacetate in benzene gives butyl glyoxalate (XIII),which is then condensed with propionaldehyde (XIV) by heating at 110 C with dibutyl-amine (D).

参考文献标题:Polyene derivatives
文献作者:Bollag,W.; et al.
参考来源:BE 0813002; FR 2223037; GB 1468401; GB 1468402


合成路线:The methylation of 2,3,5-trimethylphenol (I) with MeI and KOH in 10% aqueous ethanol gives 2,3,5-trimethylanisole (II),which is formylated with DMF and POCl3 yielding 2,3,6-trimethyl-p-anisylaldehyde (III).The condensation of (III) with acetone (B) by means of NaOH affords 4-(4-methoxy-2,3,6-trimethylphenyl)but-3-en-2-one (IV),which by a Grignard reaction with ethynylmagnesium bromide (C) in THF is converted into the acetylenic alcohol (V).Partial hydrogenation of (V) with H2 over Pd/C in hexane gives dienic alcohol (VI),which is condensed with triphenylphosphine hydrobromide in benzene affording 5-(4-methoxy-2,3,6 trimethylphenyl)-3-methylpenta-2,4-diene-1-triphenylphosphonium bromide (VII).A Wittig condensation of (VII) with butyl 3-formylcrotonate (VIII) by means of NaH in DMF gives butyl 9-(4-methoxy-2,3,6-trimethylphenyl)-3,7-dimethylnona-2,4,6,8-tetraenoate (IX),which is hydrolyzed with KOH in refluxing ethanol-water yielding the corresponding free acid (X).This acid is converted into the acyl chloride (XI) by treatment with PCl3 in refluxing benzene.Finally,this compound is treated with ethylamine (E) in ether.The butyl 3-formylcrotonate (VIII) is obtained as follows: The oxidation of dibutyl tartrate (XII) with lead tetraacetate in benzene gives butyl glyoxalate (XIII),which is then condensed with propionaldehyde (XIV) by heating at 110 C with dibutyl-amine (D).
参考文献标题:Antidandruff compositions containing 9-(4-lower alkoxy-2,3,6-trilower-alkylphenyl)-3,7-dimethyl-nona-2,4,6,8-tetraen-1-oic acid lower alkyl amides
文献作者:Bollag,W.; et al.
参考来源:DE 2542366; ES 441173; FR 2330381; GB 1504350; JP 51057840; US 4021574


产品链接: CAS No. 56281-36-8››