(R)-(2,3-dimethoxyphenyl)[1-(4-fluorophenethyl)-4-piperidinyl]methanol -Drug Synthesis Database

【结构式】

【分子编号】40494

【品名】(R)-(2,3-dimethoxyphenyl)[1-(4-fluorophenethyl)-4-piperidinyl]methanol

【CA登记号】

【分子式】C₂₂H₂₈FNO₃

【分子量】373.4676632

【元素组成】C 70.75% H 7.56% F 5.09% N 3.75% O 12.85%

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：(X)

The synthesis of MDL-100907 [11C]-labeled at the 2'-methoxy group has been reported: Condensation of 2-(4-fluorophenyl)ethyl bromide (I) with piperidine-4-carboxylic acid ethyl ester (II) by means of K2CO3 in DMF gives 1-[2-(4-fluorophenyl)ethyl]piperidine-4-carboxylic acid ethyl ester (III), which is treated with N,O-dimethylhydroxylamine and ethylmagnesium bromide in THF to yield compound (IV). Condensation of (IV) with veratrole (V) by means of BuLi in THF affords the 4-benzoylpiperidine derivative (VI), which is reduced with NaBH4 in methanol to give the racemic carbinol (VII). Optical resolution of (VII) by esterification with (S)-2-methoxy-2-phenylacetic acid (VIII) by means of DCC and DMAP in chloroform followed by column chromatography yields the diastereomer (IX), which is hydrolyzed with K2CO3 in methanol to afford MDL-100907 (X). Selective demethylation of (X) with L-selectride in THF gives the 2'-hydroxy derivative (XI), which is finally remethylated with [11C]-methyl iodide and K2CO3 in methanol.

参考文献中间体

合成目标

【1】 Mathis, C.A.; Huang, Y.Y.; Mahmood, K.; An efficient synthesis of the precursors of [11C]MDL 100907 labeled in two specific positions. J Label Compd Radiopharm 1999, 42, 10, 949.

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)	17394	1-(2-bromoethyl)-4-fluorobenzene		C₈H₈BrF	详情	详情
(II)	17410	Ethyl isonipecotate; ethyl 4-piperidinecarboxylate	1126-09-6	C₈H₁₅NO₂	详情	详情
(III)	17411	ethyl 1-(4-fluorophenethyl)-4-piperidinecarboxylate		C₁₆H₂₂FNO₂	详情	详情
(IV)	17412	1-(4-fluorophenethyl)-N-methoxy-N-methyl-4-piperidinecarboxamide		C₁₆H₂₃FN₂O₂	详情	详情
(V)	40496	tert-butyl(2-methoxyphenoxy)diphenylsilane; tert-butyl(diphenyl)silyl 2-methoxyphenyl ether		C₂₃H₂₆O₂Si	详情	详情
(VI)	17409	(2,3-dimethoxyphenyl)[1-(4-fluorophenethyl)-4-piperidinyl]methanone		C₂₂H₂₆FNO₃	详情	详情
(VII)	17399	(2,3-dimethoxyphenyl)[1-(4-fluorophenethyl)-4-piperidinyl]methanol		C₂₂H₂₈FNO₃	详情	详情
(VIII)	17400	(2S)-2-methoxy-2-phenylethanoic acid		C₉H₁₀O₃	详情	详情
(IX)	17401	(R)-(2,3-dimethoxyphenyl)[1-(4-fluorophenethyl)-4-piperidinyl]methyl (2S)-2-methoxy-2-phenylethanoate		C₃₁H₃₆FNO₅	详情	详情
(X)	40494	(R)-(2,3-dimethoxyphenyl)[1-(4-fluorophenethyl)-4-piperidinyl]methanol		C₂₂H₂₈FNO₃	详情	详情
(XI)	40495	2-[(R)-[1-(4-fluorophenethyl)-4-piperidinyl](hydroxy)methyl]-6-methoxyphenol		C₂₁H₂₆FNO₃	详情	详情

Extended Information