Etretinate, Ro-10-9359, Tegison

依曲替酯Chemical Name: (all-E)-9-(4-Methoxy-2,3,6-trimethylphenyl)-3,7-dimethyl-2,4,6,8-nonatetraenoic acid ethyl ester
CAS No. 54350-48-0
项目整合开发状态: Withdrawn
项目研究机构: Roche (Originator)
合成路线:The chloromethylation of 2,3,5-trimethylanisole (II) [prepared by alkylation of 2,3,5-trimethylphenol (I) with methyl iodide] with formaldehyde and HCl gives 4-chloromethyl-2,3,5-trimethylanisole (III),which by reaction with triphenylphosphine in refluxing toluene affords 4-methoxy-2,3,6-trimethylbenzyltriphenylphosphonium chloride (IV).The Wittig reaction of (IV) with ethyl 7-formyl-3-methylocta-2,4,6-trien-1-oate (A) affords the desired compound.

合成路线:The reaction of 2,3,5-trimethylanisole (II) [prepared by alkylation of 2,3,5-trimethylphenol (I) with methyl iodide] with DMF and POCl3 affords 4-(4-methoxy-2,3,6-trimethylbenzaldehyde (V),which is condensed with propanone (B) in aqueous NaOH giving 4-(4-methoxy-2,3,6-trimethylphenyl)-but-3-en-2-one (VI).The Grignard reaction of (VI) with ethynylmagnesium bromide (C) in THF yields 5-(4-methoxy-2,3,6-trimethylphe-nyl)-3-methyl-3-hydroxypenta-4-en-1-yne (VII),which is partially hydrogenated with H2 over deactivated Pd in hexane to give 5-(4-methoxy-2,3,6-trimethylphenyl)-3-methyl-3-hydroxypenta-1,4-diene (VIII).The reaction of (VIII) with triphenylphosphonium hydrobromide in benzene affords 5-(4-methoxy-2,3,6-trimethylphenyl)-3-methylpenta-2,4-diene-1-triphenylphosphonium bromide (IX).Finally,this compound is submitted to a Wittig reaction with ethyl 3,4-formylcrotonate (D) in DMF (NaH is used as base).