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【结 构 式】

【分子编号】43156

【品名】1-(benzyloxy)-4-bromobenzene; benzyl 4-bromophenyl ether

【CA登记号】6793-92-6

【 分 子 式 】C13H11BrO

【 分 子 量 】263.13374

【元素组成】C 59.34% H 4.21% Br 30.37% O 6.08%

与该中间体有关的原料药合成路线共 2 条

合成路线1

该中间体在本合成路线中的序号:(X)

The intermediate 4-[4-(4-aminophenyl)piperazin-1-yl]phenol (VIII) has been obtained by several related ways: 1.- The condensation of 4-bromonitrobenzene (I) with piperazine (II) gives 1-(4-nitrophenyl)piperazine (III), which is condensed with 4-bromoanisole (IV) by means of Pdo to yield 1-(4-methoxyphenyl)-4-(4-nitrophenyl)piperazine (V). Alternatively, (V) can also be obtained by condensation of (III) with 4-methoxyphenylboronic acid (VI) by means of Cu(OAc)2 in DMSO. The demethylation of (V) with HBr yields 4-[4-(4-nitrophenyl)piperazin-1-yl]phenol (VII), which is finally reduced with H2 over Pd/C to afford the target 4-[4-(4-aminophenyl)piperazin-1-yl]phenol (VIII) intermediate (see Synthline, scheme no. 22656202a, intermediate (XIV)). 2.- The condensation of piperazine (II) with 4-bromoanisole (IV) by means of Pdo gives 1-(4-methoxyphenyl)piperazine (IX), which is condensed with 4-bromonitrobenzene (I) by means of K2CO3 and tetrabutylammonium iodide (TBAI) in hot DMSO to yield intermediate 1-(4-methoxyphenyl)-4-(4-nitrophenyl)piperazine (V), already reported. 3.- The condensation of piperazine (II) with 4-(benzyloxy)phenyl bromide (X) by means of Pdo gives 1-(4-benzyloxyphenyl)piperazine (XI), which is condensed with 4-bromonitrobenzene (I) by means of K2CO3 and TBAI in hot DMSO to yield 1-(4-benzyloxyphenyl)-4-(4-nitrophenyl)piperazine (XII). The nitro group of (XII) is reduced by means of H2 (50 psi) over Pd/C in wet THF at 50? C to afford 4-[4-(4-benzyloxyphenyl)piperazin-1-yl]aniline (XIII), which is finally debenzylated with H2 (80 psi) over Pd/C in wet THF at 70? C or other drastic conditions to afford the target 4-[4-(4-aminophenyl)piperazin-1-yl]phenol (VIII) intermediate (see Synthline, scheme no. 22656202a, intermediate (XIV)). Alternatively, 1-(4-benzyloxyphenyl)-4-(4-nitrophenyl)piperazine (XII) can also be reduced directly to the target intermediate (VIII) with H2 over Pd/C under a variety of drastic conditions.

1 Hepperle, M.; Eckert, J.; Gala, D.; Shen, L.; Evans, C.A.; Goodman, A.; Mono N-arylation of piperazine(III): Metal-catalyzed N-arylation and its application to the novel preparations of the antifungal posaconazole and its advanced intermediate. Tetrahedron Lett 2002, 43, 18, 3359.
中间体序号 中间体编号 品名 CAS号 分子式 供应商 用于合成
(I) 26628 1-bromo-4-nitrobenzene 99-99-0 C6H4BrNO2 详情 详情
(II) 10355 Diethylenediamine; Piperazine 110-85-0 C4H10N2 详情 详情
(III) 20299 1-(4-nitrophenyl)piperazine 6269-89-2 C10H13N3O2 详情 详情
(IV) 63436 1-bromo-4-methoxybenzene; 4-bromophenyl methyl ether C7H7BrO 详情 详情
(V) 16314 methyl 4-[4-(4-nitrophenyl)piperazino]phenyl ether; 1-(4-methoxyphenyl)-4-(4-nitrophenyl)piperazine C17H19N3O3 详情 详情
(VI) 39246 4-methoxyphenylboronic acid 5720-07-0 C7H9BO3 详情 详情
(VII) 16345 4-[4-(4-nitrophenyl)piperazino]phenol C16H17N3O3 详情 详情
(VIII) 17110 4-[4-(4-aminophenyl)piperazino]phenol; 1-(4-Aminophenyl)-4-(4-hydroxyphenyl)piperazine; 1-(4-Hydroxyphenyl)-4-(4-aminophenyl)piperazine 74853-08-0 C16H19N3O 详情 详情
(IX) 16312 1-(4-Methoxyphenyl)piperazine; Methyl 4-piperazinophenyl ether 38212-30-5 C11H16N2O 详情 详情
(X) 43156 1-(benzyloxy)-4-bromobenzene; benzyl 4-bromophenyl ether 6793-92-6 C13H11BrO 详情 详情
(XI) 64373 1-[4-(benzyloxy)phenyl]piperazine; benzyl 4-(1-piperazinyl)phenyl ether C17H20N2O 详情 详情
(XII) 64372 benzyl 4-[4-(4-nitrophenyl)-1-piperazinyl]phenyl ether; 1-[4-(benzyloxy)phenyl]-4-(4-nitrophenyl)piperazine C23H23N3O3 详情 详情
(XIII) 64371 4-{4-[4-(benzyloxy)phenyl]-1-piperazinyl}aniline; 4-{4-[4-(benzyloxy)phenyl]-1-piperazinyl}phenylamine C23H25N3O 详情 详情

合成路线2

该中间体在本合成路线中的序号:(IV)

In an alternative procedure, lithiation of 4-(benzyloxy)-1-bromobenzene (IV), followed by addition of 1-benzyl-4-piperidone (V), gave piperidinol (VI). Subsequent treatment of (VI) with HCl produced dehydration of the tertiary alcohol and benzyl ether cleavage to give (VII). Double bond reduction and hydrogenolysis of the N-benzyl group of (VII) with H2 over Pd/C gave 4-(4-hydroxyphenyl)piperidine (VIII). This was finally alkylated with tosylate (II) to yield the title compound.

1 Guzikowski, A.P.; Acosta-Burruel, M.; Tamiz, A.P.; et al.; Synthesis of N-substituted 4-(4-hydroxyphenyl)piperidines, 4-(4-hydroxybenzyl)piperidines, and (±)-3-(4-hydroxyphenyl)pyrrolidines: Selective antagonists at the 1A/2B NMDA receptor subtype. J Med Chem 2000, 43, 5, 984.
中间体序号 中间体编号 品名 CAS号 分子式 供应商 用于合成
(II) 43154 4-phenylbutyl 4-methylbenzenesulfonate C17H20O3S 详情 详情
(IV) 43156 1-(benzyloxy)-4-bromobenzene; benzyl 4-bromophenyl ether 6793-92-6 C13H11BrO 详情 详情
(V) 15720 1-benzyltetrahydro-4(1H)-pyridinone; 1-Benzyl-4-piperidone; N-Benzyl-4-piperidone; 1-(benzyl)-4-piperidinone; 1-benzylpiperidin-4-one; 1-(benzyl)piperidin-4-one 3612-20-2 C12H15NO 详情 详情
(VI) 43157 1-benzyl-4-[4-(benzyloxy)phenyl]-4-piperidinol C25H27NO2 详情 详情
(VII) 43158 4-(1-benzyl-1,2,3,6-tetrahydro-4-pyridinyl)phenol C18H19NO 详情 详情
(VIII) 43159 4-(4-piperidinyl)phenol C11H15NO 详情 详情
Extended Information