【结 构 式】 |
【分子编号】58109 【品名】(E)-5-(4-methoxy-2,3,6-trimethylphenyl)-3-methylene-4-pentenal 【CA登记号】 |
【 分 子 式 】C16H20O2 【 分 子 量 】244.3336 【元素组成】C 78.65% H 8.25% O 13.1% |
合成路线1
该中间体在本合成路线中的序号:(X)The methylation of 2,3,5-trimethylphenol (I) with NaH and Me-I in DMSO gives 1-methoxy-2,3,5-trimethylbenzene (II), which is condensed with DMF by means of POCl3 and NaOH to yield 4-methoxy-2,3,6-trimethylbenzaldehyde (III). The condensation of benzaldehyde (III) with acetone (IV) by means of NaOH affords the butenone (V). The condensation of (V) with methyl formate by means of NaOMe in ethyl ether provides the sodium enolate (VI), which is treated with MeOH and H2SO4 to obtain the dimethylacetal (VII). The condensation of (VII) with the phosphonium bromide (VIII) by means of tBu-OK in cyclohexane gives the methylene derivative (IX), which is hydrolyzed with formic acid to yield the aldehyde (X). The isomerization of (X) by means of TEA in ethyl ether affords the 5-(4-methoxy-2,3,6-trimethylphenyl)-3-methyl-2,4-pentadienal as a mixture of (E,E) and (Z,E)-isomers that is separated by chromatography. The desired (E,E)-isomer (XI) is condensed with dimethyl isopropylidenemalonate (XII) by means of Triton B in methanol and hydrolyzed with HCl to provide the monoester (XIII), which is saponified with NaOH in methanol/water to give the malonic acid derivative (XIV). Finally, this compound is monodecarboxylated by means of pyridine in dichloromethane to yield the target Acitretin (Etretin).
【1】 Andriamialisoa, Z.; et al.; A new stereoselective synthesis of acitretin (=Soriatane(R), Neotigason(R)). Helv Chim Acta 2002, 85, 9, 2926. |
中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
---|---|---|---|---|---|---|
(I) | 33479 | 2,3,5-trimethylphenol | 697-82-5 | C9H12O | 详情 | 详情 |
(II) | 33480 | 1-methoxy-2,3,5-trimethylbenzene; methyl 2,3,5-trimethylphenyl ether | 20469-61-8 | C10H14O | 详情 | 详情 |
(III) | 33481 | 4-methoxy-2,3,6-trimethylbenzaldehyde | C11H14O2 | 详情 | 详情 | |
(IV) | 23199 | 2-Propanone; Acetone; beta-ketopropane; chevron acetone;propan-2-one; Dimethyl formaldehyde; Dimethyl ketone; dimethylketal; Ketone propane; Methyl ketone; Propanone; Pyroacetic acid; Pyroacetic ether | 67-64-1 | C3H6O | 详情 | 详情 |
(V) | 33482 | (E)-4-(4-methoxy-2,3,6-trimethylphenyl)-3-buten-2-one | 54757-47-0 | C14H18O2 | 详情 | 详情 |
(VI) | 58106 | sodium (1E,4E)-5-(4-methoxy-2,3,6-trimethylphenyl)-3-oxo-1,4-pentadien-1-olate | C15H17NaO3 | 详情 | 详情 | |
(VII) | 58107 | (E)-5,5-dimethoxy-1-(4-methoxy-2,3,6-trimethylphenyl)-1-penten-3-one | C17H24O4 | 详情 | 详情 | |
(VIII) | 30484 | Methyl(triphenyl)phosphonium bromide | 1779-49-3 | C19H18BrP | 详情 | 详情 |
(IX) | 58108 | 2-[(1E)-3-(2,2-dimethoxyethyl)-1,3-butadienyl]-5-methoxy-1,3,4-trimethylbenzene; 4-[(1E)-3-(2,2-dimethoxyethyl)-1,3-butadienyl]-2,3,5-trimethylphenyl methyl ether | C18H26O3 | 详情 | 详情 | |
(X) | 58109 | (E)-5-(4-methoxy-2,3,6-trimethylphenyl)-3-methylene-4-pentenal | C16H20O2 | 详情 | 详情 | |
(XI) | 58110 | (2E,4E)-5-(4-methoxy-2,3,6-trimethylphenyl)-3-methyl-2,4-pentadienal | C16H20O2 | 详情 | 详情 | |
(XII) | 49671 | dimethyl 2-(1-methylethylidene)malonate | 22035-53-6 | C8H12O4 | 详情 | 详情 |
(XIII) | 58111 | (2E,4E,6E,8E)-2-(methoxycarbonyl)-9-(4-methoxy-2,3,6-trimethylphenyl)-3,7-dimethyl-2,4,6,8-nonatetraenoic acid | C23H28O5 | 详情 | 详情 | |
(XIV) | 58112 | 2-[(2E,4E,6E)-7-(4-methoxy-2,3,6-trimethylphenyl)-1,5-dimethyl-2,4,6-heptatrienylidene]malonic acid | C22H26O5 | 详情 | 详情 |