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【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%

与该中间体有关的原料药合成路线共 1 条

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
Extended Information