【结 构 式】 |
【分子编号】36845 【品名】dimethyl (E,4S)-4-allyl-4-[[(benzyloxy)carbonyl]amino]-2-pentenedioate 【CA登记号】 |
【 分 子 式 】C18H21NO6 【 分 子 量 】347.36788 【元素组成】C 62.24% H 6.09% N 4.03% O 27.64% |
合成路线1
该中间体在本合成路线中的序号:(X)The cyclization of L-serine (I) with pivalaldehyde (II) by means of LDA in THF gives the oxazolidine (III), which is acylated with formic and acetic anhydride yielding the N-formyloxazolidine (IV). The reaction of (IV) with LDA affords the chiral enol (V), which is treated with allyl bromide in THF to give the chiral 4-allyloxazolidine (VI). Cleavage of the oxazolidine ring with acetyl chloride and treatment with benzyl chloroformate yields the protected chiral 2-allylserine (VII), which is oxidized with oxalyl chloride to the corresponding aldehyde (VIII). The Wittig condensation of (VIII) with triphenylphosphoranylideneacetic acid methyl ester (IX) affords the intermediate (X), which is submitted to UV irradiation with an Hanovia medium pressure mercury lamp through a Pyrex filter in benzene containing benzophenone. A mixture of isomeric bicyclic compounds from which the desired compound (XI) is isolated by column chromatography. The hydrogenation of (IX) with H2 over Pd/C in methanol provides the bicyclic aminoester (XII), which is finally hydrolyzed with 6N HCl.
【1】 von Diester, S.; et al.; Stereoselektive Alkylierung an C(alpha) von Serin, Glycerinsaure, Threonin und Weinsaure uber heterocyclische Enolate mit exocyclischer Doppelbindung. Helv Chim Acta 1987, 70, 1194-1216. |
【2】 Kozikowski, A.P.; et al.; Synthesis and biology of the conformationally restricted ACPD analogue, 2-aminobicyclo[2.1.1]hexane-2,5-dicarboxylic acid-I, a potent mGluR agonist. J Med Chem 1998, 41, 10, 1641. |
中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
---|---|---|---|---|---|---|
10101 | Benzyloxycarbonyl chloride; Benzyl chloroformate; 1-[[(Chlorocarbonyl)oxy]methyl]benzene | 501-53-1 | C8H7ClO2 | 详情 | 详情 | |
11463 | 3-Bromo-1-propene; 3-Bromopropene;allyl bromide | 106-95-6 | C3H5Br | 详情 | 详情 | |
(I) | 20915 | methyl (2S)-2-amino-3-hydroxypropanoate | 5680-80-8 | C4H9NO3 | 详情 | 详情 |
(II) | 19797 | Trimethylacetaldehyde; pivalaldehyde; 2,2-Dimethylpropionaldehyde; 2,2-Dimethylpropanal | 630-19-3 | C5H10O | 详情 | 详情 |
(III) | 36839 | methyl (4S)-2-(tert-butyl)-1,3-oxazolidine-4-carboxylate | C9H17NO3 | 详情 | 详情 | |
(IV) | 36840 | methyl (4S)-2-(tert-butyl)-3-formyl-1,3-oxazolidine-4-carboxylate | C10H17NO4 | 详情 | 详情 | |
(V) | 36841 | lithium [(2R)-2-(tert-butyl)-3-formyl-1,3-oxazolidin-4-ylidene](methoxy)methanolate | C10H16LiNO4 | 详情 | 详情 | |
(VI) | 36842 | methyl (2R,4S)-4-allyl-2-(tert-butyl)-3-formyl-1,3-oxazolidine-4-carboxylate | C13H21NO4 | 详情 | 详情 | |
(VII) | 36843 | methyl (2S)-2-[[(benzyloxy)carbonyl]amino]-2-(hydroxymethyl)-4-pentenoate | C15H19NO5 | 详情 | 详情 | |
(VIII) | 36844 | methyl (2S)-2-[[(benzyloxy)carbonyl]amino]-2-(2-oxoethyl)-4-pentenoate | C16H19NO5 | 详情 | 详情 | |
(IX) | 14689 | Methyl (triphenylphosphoranylidene)acetate; (methoxycarbonylmethylene)triphenylphosphorane;Methyl 2-(triphenyl-lambda(5)-phosphanylidene)acetate | 2605-67-6 | C21H19O2P | 详情 | 详情 |
(X) | 36845 | dimethyl (E,4S)-4-allyl-4-[[(benzyloxy)carbonyl]amino]-2-pentenedioate | C18H21NO6 | 详情 | 详情 | |
(XI) | 36846 | dimethyl (1R,2S,4R,5S)-2-[[(benzyloxy)carbonyl]amino]bicyclo[2.1.1]hexane-2,5-dicarboxylate | C18H21NO6 | 详情 | 详情 | |
(XII) | 36847 | dimethyl (1R,2S,4R,5S)-2-aminobicyclo[2.1.1]hexane-2,5-dicarboxylate | C10H15NO4 | 详情 | 详情 |