【结 构 式】 |
【分子编号】25162 【品名】2-benzyl-3,5-bis(benzyloxy)benzaldehyde 【CA登记号】 |
【 分 子 式 】C28H24O3 【 分 子 量 】408.49676 【元素组成】C 82.33% H 5.92% O 11.75% |
合成路线1
该中间体在本合成路线中的序号:(IX)Alkylation of methyl 3,5-dihydroxybenzoate (I) with benzyl bromide in the presence of NaH gave dibenzyl ether (II). Subsequent basic hydrolysis of the ester function of (II) provided carboxylic acid (III). This was protected as the oxazoline (VI) via conversion into acid chloride with SOCl2, followed by coupling with 2-amino-2-methyl-1-propanol (IV), and then cyclization of the hydroxy amide (V) with SOCl2. After lithiation of (VI) with n-BuLi at -78 C, the 2-benzyl substituent was introduced by treatment with benzyl bromide to afford (VII). Quaternization of (VII) with boiling CH3I provided iminium salt (VIII), which was reduced with NaBH4 and then hydrolyzed to aldehyde (IX). Hydantoin (X) was then prepared from (IX) under Bucherer-Bergs conditions in the presence of KCN and (NH4)2CO3. Finally, hydrogenolytic cleavage of the O-benzyl groups, of (X) yielded (XI), which by basic hydrolysis of the hydantoin ring provided the title amino acid.
【1】 Baker, S.R.; et al.; Synthesis and pharmacological evaluation of benzamides as selective 5-HT4 receptor agonists. 15th European Federation for Medicinal Chemistry International Symposium on Medicinal Chemistry (Sept 6 1998, Edinburgh) 1998, Abs P 270. |
【2】 Baker, S.R.; Clark, B.P.; Goldsworthy, J.; Harris, J.R. (Eli Lilly and Company); Derivs. of phenylglycine and use thereof as pharmaceuticals. EP 0807621; JP 1998067723; US 5863947 . |
中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
---|---|---|---|---|---|---|
12912 | 1-(Bromomethyl)benzene; Alpha-bromotoluene | 100-39-0 | C7H7Br | 详情 | 详情 | |
(I) | 25155 | methyl 3,5-dihydroxybenzoate | 2150-44-9 | C8H8O4 | 详情 | 详情 |
(II) | 25156 | methyl 3,5-bis(benzyloxy)benzoate | C22H20O4 | 详情 | 详情 | |
(III) | 25157 | 3,5-bis(benzyloxy)benzoic acid | 28917-43-3 | C21H18O4 | 详情 | 详情 |
(IV) | 21513 | 2-amino-2-methyl-1-propanol;Karl Fischer;2-Amino-2-methyl-propan-1-ol;2-amino-2-methyl-1-propanol | 124-68-5 | C4H11NO | 详情 | 详情 |
(V) | 25158 | 3,5-bis(benzyloxy)-N-(2-hydroxy-1,1-dimethylethyl)benzamide | C25H27NO4 | 详情 | 详情 | |
(VI) | 25159 | benzyl 3-(benzyloxy)-5-(4,4-dimethyl-4,5-dihydro-1,3-oxazol-2-yl)phenyl ether | C25H25NO3 | 详情 | 详情 | |
(VII) | 25160 | 2-[2-benzyl-3,5-bis(benzyloxy)phenyl]-4,4-dimethyl-4,5-dihydro-1,3-oxazole | C32H31NO3 | 详情 | 详情 | |
(VIII) | 25161 | 2-[2-benzyl-3,5-bis(benzyloxy)phenyl]-3,4,4-trimethyl-4,5-dihydro-1,3-oxazol-3-ium iodide | C33H34INO3 | 详情 | 详情 | |
(IX) | 25162 | 2-benzyl-3,5-bis(benzyloxy)benzaldehyde | C28H24O3 | 详情 | 详情 | |
(X) | 25163 | 5-[2-benzyl-3,5-bis(benzyloxy)phenyl]-2,4-imidazolidinedione | C30H26N2O4 | 详情 | 详情 | |
(XI) | 25164 | 5-(2-benzyl-3,5-dihydroxyphenyl)-2,4-imidazolidinedione | C16H14N2O4 | 详情 | 详情 |