4-{2-[(diphenylmethyl)oxy]ethyl}-1-[(4-fluorophenyl)methyl]-3-piperidinyl 4,7,7-trimethyl-3-oxo-2-oxabicyclo[2.2.1]heptane-1-carboxylate -Drug Synthesis Database

【结构式】

【分子编号】63537

【品名】4-{2-[(diphenylmethyl)oxy]ethyl}-1-[(4-fluorophenyl)methyl]-3-piperidinyl 4,7,7-trimethyl-3-oxo-2-oxabicyclo[2.2.1]heptane-1-carboxylate

【CA登记号】

【分子式】C₃₇H₄₂FNO₅

【分子量】599.7426232

【元素组成】C 74.1% H 7.06% F 3.17% N 2.34% O 13.34%

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：(IX)

Alkylation of 2-pyridin-4-ylethanol (I) with 4-fluorobenzyl chloride (II), followed by reduction of the resultant pyridinium salt (III) with NaBH4 leads to the tetrahydropyridine (IV). Acid-catalyzed condensation of alcohol (IV) with benzhydrol (V) then provides the benzhydryl ether (VI) (1). Hydroboration of tetrahydropyridine (VI) and subsequent oxidative work up gives rise to the racemic trans piperidinol rac-(VII) (1,2). Resolution of (VII) is accomplished via esterification with (-)-camphanic chloride (VIII), followed by HPLC separation of the resulting diastereoisomers. The desired isomer (IX) is finally hydrolyzed employing K2CO3 in MeOH to provide the target enantiomer

参考文献中间体

合成目标

【1】 Ghorai, S.K.; Cook, C.; Davis, M.; Venkataraman, S.K.; George, C.; Beardsley, P.M.; Reith, M.E.A.; Dutta, A.K.; High affinity hydroxypiperidine analogues of 4-(2-benzhydryloxyethyl)-1-(4-fluorobenzyl)piperidine for the dopamine transporter: Stereospecific interactions in vitro and in vivo. J Med Chem 2003, 46, 7, 1220.
【2】 Dutta, A.K. (Wayne State University); N- and O-substd. 4-[2-(diphenylmethoxy)-ethyl]-1-[(phenyl)methyl]piperidine analogs and methods of treating CNS disorders therewith. WO 0198266 .

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)	52533	2-(4-Pyridinyl)-1-ethanol; 2-Pyridin-4-ylethanol		C₇H₉NO	详情	详情
(II)	12354	4-Fluorobenzyl chloride; 1-(Chloromethyl)-4-fluorobenzene	352-11-4	C₇H₆ClF	详情	详情
(III)	63533	1-[(4-fluorophenyl)methyl]-4-(2-hydroxyethyl)pyridinium chloride		C₁₄H₁₅ClFNO	详情	详情
(IV)	63534	2-{1-[(4-fluorophenyl)methyl]-1,2,3,6-tetrahydro-4-pyridinyl}-1-ethanol		C₁₄H₁₈FNO	详情	详情
(V)	11845	Diphenylmethanol; Benzhydrol	91-01-0	C₁₃H₁₂O	详情	详情
(VI)	63535	diphenylmethyl 2-{1-[(4-fluorophenyl)methyl]-1,2,3,6-tetrahydro-4-pyridinyl}ethyl ether; 4-{2-[(diphenylmethyl)oxy]ethyl}-1-[(4-fluorophenyl)methyl]-1,2,3,6-tetrahydropyridine		C₂₇H₂₈FNO	详情	详情
(VII)	63536	4-{2-[(diphenylmethyl)oxy]ethyl}-1-[(4-fluorophenyl)methyl]-3-piperidinol		C₂₇H₃₀FNO₂	详情	详情
(VIII)	16583	(1S,4R)-4,7,7-trimethyl-3-oxo-2-oxabicyclo[2.2.1]heptane-1-carbonyl chloride; (-)-Camphanic chloride	39637-74-6	C₁₀H₁₃ClO₃	详情	详情
(IX)	63537	4-{2-[(diphenylmethyl)oxy]ethyl}-1-[(4-fluorophenyl)methyl]-3-piperidinyl 4,7,7-trimethyl-3-oxo-2-oxabicyclo[2.2.1]heptane-1-carboxylate		C₃₇H₄₂FNO₅	详情	详情

Extended Information