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【结 构 式】

【分子编号】56457

【品名】methyl (3S,4R)-4-(4-fluorophenyl)-1-methyl-3-piperidinecarboxylate

【CA登记号】

【 分 子 式 】C14H18FNO2

【 分 子 量 】251.3008632

【元素组成】C 66.91% H 7.22% F 7.56% N 5.57% O 12.73%

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:(VII)

The hydrogenation of 4-(4-fluorophenyl)-3-(ethoxycarbonyl)-1-methylpyridinium bromide (I) with H2 over PtO2 in toluene/ethanol gives racemic (cis)-4-(4-fluorophenyl)-1-methylpiperidine-3-carboxylic acid methyl ester (rac)-(II), which is isomerized with NaOMe in refluxing toluene to yield the trans-isomer (rac)-(III). The reduction of (rac)-(III) with LiAlH4 in toluene/THF affords the hydroxymethyl compound (rac)-(IV), which is submitted to optical resolution with L-(-)-di-p-toluoyltartaric acid to provide the chiral (3S,4R)-(V). Alternatively, the optical resolution of (cis)-(rac)-(II) with D-(+)-di-p-toluoyltartaric acid gives the ester (cis)-(3R,4R)-(VI), which is isomerized with NaOMe in refluxing toluene to yield ester (trans)-(3S,4R)-(VII). Finally, this compound is reduced with LiAlH4 in toluene/THF to afford the previously reported intermediate (3S,4R)-(V). The reaction of (3S,4R)-(V) with benzenesulfonyl chloride (VIII) and dimethylethylamine in toluene gives the corresponding sulfonate (3S,4R)-(IX), which is condensed with 5-hydroxy-1,3-benzodioxole (X) by means of NaOMe in hot DMF to yield the adduct (3S,4R)-(XI). Finally, this compound is demethylated by reaction with phenyl chloroformate (XII) to afford the cyclic carbamate (3S,4R)-(XIII), which is hydrolyzed with KOH in refluxing toluene.

1 Borrett, G.T.; Ward, N.; Crowe, D.; Wells, A.S. (GlaxoSmithKline plc); Process for the preparation of paroxetine. WO 0129031 .
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) 56453 4-(4-fluorophenyl)-3-(methoxycarbonyl)-1-methylpyridinium bromide C14H13BrFNO2 详情 详情
(II) 56454 (rac)-methyl (3R,4R)-4-(4-fluorophenyl)-1-methyl-3-piperidinecarboxylate C14H18FNO2 详情 详情
(III) 56455 (rac)-methyl (3S,4R)-4-(4-fluorophenyl)-1-methyl-3-piperidinecarboxylate C14H18FNO2 详情 详情
(IV) 43487 [(3S,4R)-4-(4-fluorophenyl)-1-methylpiperidinyl]methanol; trans-(3S)-4-(4-fluorophenyl)-1-methyl-3-piperidine methanol 105812-81-5 C13H18FNO 详情 详情
(V) 56458 [(3S,4R)-4-(4-fluorophenyl)-1-methylpiperidinyl]methanol C13H18FNO 详情 详情
(VI) 56456 methyl (3R,4R)-4-(4-fluorophenyl)-1-methyl-3-piperidinecarboxylate C14H18FNO2 详情 详情
(VII) 56457 methyl (3S,4R)-4-(4-fluorophenyl)-1-methyl-3-piperidinecarboxylate C14H18FNO2 详情 详情
(VIII) 14713 benzenesulfonyl chloride 98-09-9 C6H5ClO2S 详情 详情
(IX) 10986 [(3S,4R)-4-(4-fluorophenyl)-1-methylhexahydro-3-pyridinyl]methyl benzenesulfonate C19H22FNO3S 详情 详情
(X) 10985 1,3-Benzodioxol-5-ol; Sesamol 533-31-3 C7H6O3 详情 详情
(XI) 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
(XII) 13580 1-[(Chlorocarbonyl)oxy]benzene; phenyl chloroformate 1885-14-9 C7H5ClO2 详情 详情
(XIII) 43489 phenyl (3S,4R)-3-[(1,3-benzodioxol-5-yloxy)methyl]-4-(4-fluorophenyl)-1-piperidinecarboxylate C26H24FNO5 详情 详情
Extended Information