[4-(4-fluorophenyl)-1-methyl-1,2,3,6-tetrahydro-3-pyridinyl]methanol -Drug Synthesis Database

【结构式】

【分子编号】45034

【品名】[4-(4-fluorophenyl)-1-methyl-1,2,3,6-tetrahydro-3-pyridinyl]methanol

【CA登记号】

【分子式】C₁₃H₁₆FNO

【分子量】221.2745832

【元素组成】C 70.57% H 7.29% F 8.59% N 6.33% O 7.23%

与该中间体有关的原料药合成路线共 1 条

合成路线1

该中间体在本合成路线中的序号：(III)

A synthesis of [14C]-paroxetine labeled at the -CH2O- group has been described: 4-(4-Fluorophenyl)-1-methyl-1,2,5,6-tetrahydropyridine (I) is hydroxymethylated with [14C]-formaldehyde (II), yielding 4-(4-fluorophenyl)-1-methyl-1,2,5,6-tetrahydropyridine-3-methanol (III), which is hydrogenated with H2 over Pd/C in ethanol to give 4-(4-fluorophenyl)-1-methylpiperidine-3-methanol (IV) as a mixture of cis- and trans-isomers. The reaction of (IV) with phenylsulfonyl chloride and NaOH in water affords the corresponding sulfonate (V), which is then condensed with 3,4-(methylenedioxy)phenol (VI) by means of NaOH in toluene-4-methyl-2-pentanol, giving 4-(4-fluorophenyl)-1-methyl-3-[3,4-(methylenedioxy)phenoxymethyl]piperi dine (VII). The chromatographic separation of the trans-isomer of (VII), followed by its optical resolution with L-(+)-tartaric acid, affords optically pure (-)-(3S,4R)-N-methylparoxetine (VIII), which is finally demethylated with vinyl chloroformate and dry HCl.

参考文献中间体

合成目标

【1】 Willcocks, K.; Rustidge, D.C.; Barnes, R.D.; Tidy, D.J.D.; The synthesis of [14C]-3S,4R-4-(4-fluorophenyl)-3-(3,4-methylenedioxyp henoxymethyl)piperidine hydrochloride (BRL 29060A), and mechanistic studies using carbon-13 labelling. J Label Compd Radiopharm 1993, 33, 8, 783.

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(IV cis+trans)	10991	[4-(4-Fluorophenyl)-1-methyl-3-piperidinyl]methanol		C₁₃H₁₈FNO	详情	详情
(V cis+trans)	10992	[4-(4-fluorophenyl)-1-methyl-3-piperidinyl]methyl benzenesulfonate		C₁₉H₂₂FNO₃S	详情	详情
(IV cis+trans)	45035	[4-(4-fluorophenyl)-1-methyl-3-piperidinyl]methanol		C₁₃H₁₈FNO	详情	详情
(V cis+trans)	45036	[4-(4-fluorophenyl)-1-methyl-3-piperidinyl]methyl benzenesulfonate		C₁₉H₂₂FNO₃S	详情	详情
(I)	10989	4-(4-Fluorophenyl)-1-methyl-1,2,3,6-tetrahydropyridine		C₁₂H₁₄FN	详情	详情
(III)	10990	[4-(4-Fluorophenyl)-1-methyl-1,2,3,6-tetrahydro-3-pyridinyl]methanol		C₁₃H₁₆FNO	详情	详情
(III)	45034	[4-(4-fluorophenyl)-1-methyl-1,2,3,6-tetrahydro-3-pyridinyl]methanol		C₁₃H₁₆FNO	详情	详情
(VI)	10985	1,3-Benzodioxol-5-ol; Sesamol	533-31-3	C₇H₆O₃	详情	详情
(VII)	10994	1,3-Benzodioxol-5-yl [4-(4-fluorophenyl)-1-methyl-3-piperidinyl]methyl ether; 3-[(1,3-Benzodioxol-5-yloxy)methyl]-4-(4-fluorophenyl)-1-methylpiperidine		C₂₀H₂₂FNO₃	详情	详情
(VII)	45037	1,3-benzodioxol-5-yl [4-(4-fluorophenyl)-1-methyl-3-piperidinyl]methyl ether; 3-[(1,3-benzodioxol-5-yloxy)methyl]-4-(4-fluorophenyl)-1-methylpiperidine		C₂₀H₂₂FNO₃	详情	详情
(VIII)	10987	(3S,4R)-3-[(1,3-Benzodioxol-5-yloxy)methyl]-4-(4-fluorophenyl)-1-methylhexahydropyridine; 1,3-Benzodioxol-5-yl [(3S,4R)-4-(4-fluorophenyl)-1-methylhexahydro-3-pyridinyl]methyl ether		C₂₀H₂₂FNO₃	详情	详情
(VIII)	45038	(3S,4R)-3-[(1,3-benzodioxol-5-yloxy)methyl]-4-(4-fluorophenyl)-1-methylpiperidine; 1,3-benzodioxol-5-yl [(3S,4R)-4-(4-fluorophenyl)-1-methylpiperidinyl]methyl ether		C₂₀H₂₂FNO₃	详情	详情

Extended Information