【结 构 式】 |
【分子编号】33488 【品名】(2E,4E,6E,8E)-9-(4-methoxy-2,3,6-trimethylphenyl)-3,7-dimethyl-2,4,6,8-nonatetraenoic acid 【CA登记号】 |
【 分 子 式 】C21H26O3 【 分 子 量 】326.43564 【元素组成】C 77.27% H 8.03% O 14.7% |
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 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).
【1】 Bollag, W.; et al.; Polyene derivatives. BE 0813002; FR 2223037; GB 1468401; GB 1468402 . |
【2】 Bollag, W.; et al.; 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. DE 2542366; ES 441173; FR 2330381; GB 1504350; JP 51057840; US 4021574 . |
【3】 Castaner, J.; Hillier, K.; Motretinide. Drugs Fut 1978, 3, 2, 126. |
中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
---|---|---|---|---|---|---|
(E) | 10928 | Ethanamine | 75-04-7 | C2H7N | 详情 | 详情 |
(B) | 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 |
(A) | 33491 | Dimethylformamide | 68-12-2 | C3H7NO | 详情 | 详情 |
(D) | 33492 | N,N-dibutylamine; N-butyl-1-butanamine | 111-92-2 | C8H19N | 详情 | 详情 |
(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) | 33482 | (E)-4-(4-methoxy-2,3,6-trimethylphenyl)-3-buten-2-one | 54757-47-0 | C14H18O2 | 详情 | 详情 |
(V) | 33483 | (E)-1-(4-methoxy-2,3,6-trimethylphenyl)-3-methyl-1-penten-4-yn-3-ol | C16H20O2 | 详情 | 详情 | |
(VI) | 33484 | (1E)-1-(4-methoxy-2,3,6-trimethylphenyl)-3-methyl-1,4-pentadien-3-ol | C16H22O2 | 详情 | 详情 | |
(VII) | 33485 | [(2E,4E)-5-(4-methoxy-2,3,6-trimethylphenyl)-3-methyl-2,4-pentadienyl](triphenyl)phosphonium bromide | C34H36BrOP | 详情 | 详情 | |
(VIII) | 33486 | butyl (E)-3-methyl-4-oxo-2-butenoate | C9H14O3 | 详情 | 详情 | |
(IX) | 33487 | butyl (2E,4E,6E,8E)-9-(4-methoxy-2,3,6-trimethylphenyl)-3,7-dimethyl-2,4,6,8-nonatetraenoate | C25H34O3 | 详情 | 详情 | |
(X) | 33488 | (2E,4E,6E,8E)-9-(4-methoxy-2,3,6-trimethylphenyl)-3,7-dimethyl-2,4,6,8-nonatetraenoic acid | C21H26O3 | 详情 | 详情 | |
(XI) | 33489 | (2E,4E,6E,8E)-9-(4-methoxy-2,3,6-trimethylphenyl)-3,7-dimethyl-2,4,6,8-nonatetraenoyl chloride | C21H25ClO2 | 详情 | 详情 | |
(XII) | 33490 | Dibutyl tartrate | 87-92-3 | C12H22O6 | 详情 | 详情 |
(XIII) | 30937 | butyl 2-oxoacetate | C6H10O3 | 详情 | 详情 | |
(XIV) | 15966 | propionaldehyde | 123-38-6 | C3H6O | 详情 | 详情 |
(C) | 17778 | ETHYNYLMAGNESIUM BROMIDE; bromo(ethynyl)magnesium | 4301-14-8 | C2HBrMg | 详情 | 详情 |