1-[(3-bromopropoxy)methyl]benzene -Drug Synthesis Database

【结构式】

【分子编号】28080

【品名】1-[(3-bromopropoxy)methyl]benzene

【CA登记号】

【分子式】C₁₀H₁₃BrO

【分子量】229.11662

【元素组成】C 52.42% H 5.72% Br 34.87% O 6.98%

与该中间体有关的原料药合成路线共 2 条

合成路线1 合成路线2

合成路线1

该中间体在本合成路线中的序号：(V)

The intermediate 1-(4-fluorophenyl)-1-(3-hydroxypropyl)-1,3-dihydroisobenzofuran-5-carbonitrile (IV) has been obtained by three related ways: 1. The condensation of 1-(4-fluorophenyl)-1,3-dihydroisobenzofuran-5-carbonitrile (I) with 3-(tert-butyldimethylsilyloxy)propyl bromide (II) by means of LDA in THF gives 1-[3-(tert-butyldimethylsilyloxy)propyl]-1-(4-fluorophenyl)-1,3-dihydroisobenzofuran-5-carbonitrile (III), which is deprotected with HCl in methanol to yield the hydroxypropyl intermediate (IV). 2. The condensation of 1-(4-fluorophenyl)-1,3-dihydroisobenzofuran-5-carbonitrile (I) with 3-(benzyloxy)propyl bromide (V) by means of LDA in THF gives 1-[3-(benzyloxy)propyl]-1-(4-fluorophenyl)-1,3-dihydroisobenzofuran-5-carbonitrile (VI), which is deprotected by treatment with 1,4-cyclohexadiene over Pd/C in ethanol to yield the hydroxypropyl intermediate (IV). 3. The condensation of 1-(4-fluorophenyl)-1,3-dihydroisobenzofuran-5-carbonitrile (I) with 3-(tetrahydropyranyloxy)propyl bromide (VII) by means of LDA in THF gives 1-(4-fluorophenyl)-1-[3-(tetrahydropyranyloxy)propyl]-1,3-dihydroisobenzofuran-5-carbonitrile (VIII), which is deprotected with Ts-OH in methanol to yield the hydroxypropyl intermediate (IV). The reaction of the intermediate (IV) with Ts-Cl and TEA in toluene gives the corresponding tosylate (IX), which is finally treated with dimethylamine in hot DMF to afford the target citalopram. The reaction of the intermediate (IV) with Ms-Cl and TEA in THF gives the corresponding mesylate (X), which is finally treated with dimethylamine in hot ethanol/THF to afford the target citalopram. Alternatively, the reaction of mesylate (X) with NaN3 in hot DMF gives the corresponding azido compound (XI), which is hydrogenated with H2 over Pd/C in EtOH to yield the 3-aminopropyl derivative (XII). Finally, this compound is methylated by means of formaldehyde and NaCNBH3 in methanol to provide the target citalopram.

参考文献中间体

合成目标

【1】 Petersen, H.; Rock, M.H.; Ahmadian, H. (H. Lundbeck A/S); Method for the preparation of citalopram. US 6420574 .

中间体序号	中间体编号	品名	分子式	供应商	用于合成
(I)	33233	1-(4-fluorophenyl)-5-phtalancarbonitrile; 1-(4-fluorophenyl)-1,3-dihydro-2-benzofuran-5-carbonitrile	C₁₅H₁₀FNO	详情	详情
(II)	30994	3-bromopropyl tert-butyl(dimethyl)silyl ether; (3-bromopropoxy)(tert-butyl)dimethylsilane	C₉H₂₁BrOSi	详情	详情
(III)	55297	1-(3-{[tert-butyl(dimethyl)silyl]oxy}propyl)-1-(4-fluorophenyl)-1,3-dihydro-2-benzofuran-5-carbonitrile	C₂₄H₃₀FNO₂Si	详情	详情
(IV)	55298	1-(4-fluorophenyl)-1-(3-hydroxypropyl)-1,3-dihydro-2-benzofuran-5-carbonitrile	C₁₈H₁₆FNO₂	详情	详情
(V)	28080	1-[(3-bromopropoxy)methyl]benzene	C₁₀H₁₃BrO	详情	详情
(VI)	55299	1-[3-(benzyloxy)propyl]-1-(4-fluorophenyl)-1,3-dihydro-2-benzofuran-5-carbonitrile	C₂₅H₂₂FNO₂	详情	详情
(VII)	42252	3-bromopropyl tetrahydro-2H-pyran-2-yl ether; 2-(3-bromopropoxy)tetrahydro-2H-pyran	C₈H₁₅BrO₂	详情	详情
(VIII)	55300	1-(4-fluorophenyl)-1-[3-(tetrahydro-2H-pyran-2-yloxy)propyl]-1,3-dihydro-2-benzofuran-5-carbonitrile	C₂₃H₂₄FNO₃	详情	详情
(IX)	55301	3-[5-cyano-1-(4-fluorophenyl)-1,3-dihydro-2-benzofuran-1-yl]propyl 4-methylbenzenesulfonate	C₂₅H₂₂FNO₄S	详情	详情
(X)	55302	3-[5-cyano-1-(4-fluorophenyl)-1,3-dihydro-2-benzofuran-1-yl]propyl methanesulfonate	C₁₉H₁₈FNO₄S	详情	详情
(XI)	55303	1-(3-azidopropyl)-1-(4-fluorophenyl)-1,3-dihydro-2-benzofuran-5-carbonitrile	C₁₈H₁₅FN₄O	详情	详情
(XII)	55304	1-(3-aminopropyl)-1-(4-fluorophenyl)-1,3-dihydro-2-benzofuran-5-carbonitrile	C₁₈H₁₇FN₂O	详情	详情

合成路线2

该中间体在本合成路线中的序号：(V)

Iodophenylpentadecanoic acid (I) was reduced to the corresponding alcohol (II) with borane in THF and then converted to the tosylate (III). Treatment of 3-(benzyloxy)propanol (IV) with CBr4 and PPh3 afforded bromide (V). This was treated with Mg in THF and the resulting Grignard reagent was coupled with tosylate (III) in the presence of Li2CuCl4 to provide octadecyl benzyl ether (VI), which was cleaved to the aryl octadecanol (VII) using AlCl3 and anisole. Reaction of alcohol (VII) with phospholane (VIII), followed by condensation with trimethylamine then furnished the title compound.

参考文献中间体

合成目标

【1】 Weichert, J.P.; Rampy, M.A.; Counsell, R.E.; Longino, M.A.; Pinchuk, A.N. (University of Michigan); Radioiodinated phospholipid ether analogs and methods of using the same. WO 9824480 .

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)	28077	15-(4-iodophenyl)pentadecanoic acid		C₂₁H₃₃IO₂	详情	详情
(II)	28078	15-(4-iodophenyl)-1-pentadecanol		C₂₁H₃₅IO	详情	详情
(III)	28079	15-(4-iodophenyl)pentadecyl 4-methylbenzenesulfonate		C₂₈H₄₁IO₃S	详情	详情
(IV)	14687	3-(benzyloxy)-1-propanol; 3-(Benzyloxy)propanol	4799-68-2	C₁₀H₁₄O₂	详情	详情
(V)	28080	1-[(3-bromopropoxy)methyl]benzene		C₁₀H₁₃BrO	详情	详情
(VI)	28081	benzyl 18-(4-iodophenyl)octadecyl ether		C₃₁H₄₇IO	详情	详情
(VII)	28081	benzyl 18-(4-iodophenyl)octadecyl ether		C₃₁H₄₇IO	详情	详情
(VIII)	28082	18-(4-iodophenyl)-1-octadecanol		C₂₄H₄₁IO	详情	详情

Extended Information