【结 构 式】 |
【分子编号】61895 【品名】3-[(benzyloxy)methyl]cyclobutanone 【CA登记号】 |
【 分 子 式 】C12H14O2 【 分 子 量 】190.24196 【元素组成】C 75.76% H 7.42% O 16.82% |
合成路线1
该中间体在本合成路线中的序号:(III)A synthesis leading to the pure anti isomer has also been reported. Cycloaddition of dichloroketene, generated in situ from trichloroacetyl chloride and Zn-Cu couple, to allyl benzyl ether (I) produces the dichloro cyclobutanone (II). Subsequent reduction of the dichloro compound (II) with Zn dust in AcOH gives 3-(benzyloxymethyl)cyclobutanone (III). Reaction of cyclobutanone (III) with KCN and (NH4)2CO3 furnishes a mixture of the isomeric hydantoins (IV) and (V), separable by column chromatography. The minor anti isomer (V) is subsequently hydrolyzed under alkaline conditions to provide aminoacid (VI). After protection of (VI) as the N-Boc derivative (VII), treatment with t-butyl trichloroacetimidate gives the tert-butyl ester (VIII). Removal of the O-benzyl group of (VIII) by catalytic hydrogenolysis, followed by treatment of the resultant alcohol (IX) with methanesulfonyl chloride provides mesylate (X). The mesylate group of (X) is then displaced with [18F]-potassium fluoride to afford the [18F]-labeled fluoride (XI). Finally, acidic hydrolysis of the N-Boc amino ester (XI) yields the title radiofluorinated compound.
【1】 Martarello, L.; et al.; Synthesis of syn- and anti-1-amino-3-[18F]fluoromethyl-cyclobutane-1-carboxylic acid (FMACBC9, potential PET ligands for tumor detection. J Med Chem 2002, 45, 11, 2250. |
中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
---|---|---|---|---|---|---|
(A) | 61667 | tert-butyl 2,2,2-trichloroethanimidoate | C6H10Cl3NO | 详情 | 详情 | |
(I) | 61893 | 1-[(allyloxy)methyl]benzene; allyl benzyl ether | 14593-43-2 | C10H12O | 详情 | 详情 |
(II) | 61894 | 3-[(benzyloxy)methyl]-2,2-dichlorocyclobutanone | C12H12Cl2O2 | 详情 | 详情 | |
(III) | 61895 | 3-[(benzyloxy)methyl]cyclobutanone | C12H14O2 | 详情 | 详情 | |
(IV) | 61896 | 2-[(benzyloxy)methyl]-5,7-diazaspiro[3.4]octane-6,8-dione | C14H16N2O3 | 详情 | 详情 | |
(V) | 61897 | 2-[(benzyloxy)methyl]-5,7-diazaspiro[3.4]octane-6,8-dione | C14H16N2O3 | 详情 | 详情 | |
(VI) | 61898 | 1-amino-3-[(benzyloxy)methyl]cyclobutanecarboxylic acid | C13H17NO3 | 详情 | 详情 | |
(VII) | 61899 | 3-[(benzhydryloxy)methyl]-1-[(tert-butoxycarbonyl)amino]cyclobutanecarboxylic acid | C24H29NO5 | 详情 | 详情 | |
(VIII) | 61900 | tert-butyl 3-[(benzhydryloxy)methyl]-1-[(tert-butoxycarbonyl)amino]cyclobutanecarboxylate | C28H37NO5 | 详情 | 详情 | |
(IX) | 61942 | tert-butyl 1-[(tert-butoxycarbonyl)amino]-3-(hydroxymethyl)cyclobutanecarboxylate | C15H27NO5 | 详情 | 详情 | |
(X) | 61943 | tert-butyl 1-[(tert-butoxycarbonyl)amino]-3-{[(methylsulfonyl)oxy]methyl}cyclobutanecarboxylate | C16H29NO7S | 详情 | 详情 | |
(XI) | 61944 | tert-butyl 1-[(tert-butoxycarbonyl)amino]-3-(fluoromethyl)cyclobutanecarboxylate | C15H26FNO4 | 详情 | 详情 |