3-chloro-1-phenyl-1-propanol -Drug Synthesis Database

【结构式】

【分子编号】28074

【品名】3-chloro-1-phenyl-1-propanol

【CA登记号】

【分子式】C₉H₁₁ClO

【分子量】170.63844

【元素组成】C 63.35% H 6.5% Cl 20.78% O 9.38%

与该中间体有关的原料药合成路线共 4 条

合成路线1 合成路线2 合成路线3 合成路线4

合成路线1

该中间体在本合成路线中的序号：(II)

A new synthesis of tomoxetine has been described: The reduction of omega-chloropropiophenone (I) with NaBH4 in ethanol gives 3-chloro-1-phenyl-1-propanol (II), which is treated with butyric anhydride and pyridine in dichloromethane to yield the corresponding racemic ester (III). The optical resolution of (III) with immobilized lipase B from Candida antarctica (CALB) affords a mixture of unreacted (S)-ester and (R)-alcohol (IV) that are separated by column chromatography. Condensation of th (R)-alcohol (IV) with 2-methylphenol (V) by means of PPh3 and diethyl azodicarboxylate (DEAD) in THF gives the corresponding ether (VI), which is finally treated with methylamine in refluxing ethanol.

参考文献中间体

合成目标

【1】 Anthonsen, T.; Ho, B.H.; Liu, H.L.; Chemoenzymatic synthesis of the non-tricyclic antidepressants fluoxetine, tomoxetine and nisoxetine. J Chem Soc - Perkins Trans I 2000, 11, 11, 1767.

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)	28073	3-chloro-1-phenyl-1-propanone	936-59-4	C₉H₉ClO	详情	详情
(II)	28074	3-chloro-1-phenyl-1-propanol		C₉H₁₁ClO	详情	详情
(III)	37781	3-chloro-1-phenylpropyl butyrate		C₁₃H₁₇ClO₂	详情	详情
(IV)	37782	(1R)-3-chloro-1-phenyl-1-propanol		C₉H₁₁ClO	详情	详情
(V)	10010	o-Cresol	95-48-7	C₇H₈O	详情	详情
(VI)	44328	(1R)-3-chloro-1-phenylpropyl 2-methylphenyl ether; 1-[[(1R)-3-chloro-1-phenylpropyl]oxy]-2-methylbenzene	114446-47-8	C₁₆H₁₇ClO	详情	详情

合成路线2

该中间体在本合成路线中的序号：(II)

The reduction of omega-chloropropiophenone (I) with NaBH4 in ethanol gives 3-chloro-1-phenyl-1-propanol (II), which is treated with butyric anhydride and pyridine in dichloromethane, yielding the corresponding racemic ester (III). The optical resolution of (III) with immobilized lipase B from Candida antarctica (CALB) affords a mixture of unreacted (S)-ester and (R)-alcohol (IV), which are separated by column chromatography. The condensation of alcohol (IV) with 4-(trifluoromethyl)phenol (V) by means of PPh3 and diethyl azodicarboxylate (DEAD) in THF gives the corresponding ether (VI), which is finally treated with methylamine in refluxing ethanol.

参考文献中间体

合成目标

【1】 Anthonsen, T.; Ho, B.H.; Liu, H.L.; Chemoenzymatic synthesis of the non-tricyclic antidepressants fluoxetine, tomoxetine and nisoxetine. J Chem Soc - Perkins Trans I 2000, 11, 11, 1767.

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)	28073	3-chloro-1-phenyl-1-propanone	936-59-4	C₉H₉ClO	详情	详情
(II)	28074	3-chloro-1-phenyl-1-propanol		C₉H₁₁ClO	详情	详情
(III)	37781	3-chloro-1-phenylpropyl butyrate		C₁₃H₁₇ClO₂	详情	详情
(IV)	37782	(1R)-3-chloro-1-phenyl-1-propanol		C₉H₁₁ClO	详情	详情
(V)	33607	4-(trifluoromethyl)phenol	402-45-9	C₇H₅F₃O	详情	详情
(VI)	43106	1-[[(1R)-3-chloro-1-phenylpropyl]oxy]-4-(trifluoromethyl)benzene; (1R)-3-chloro-1-phenylpropyl 4-(trifluoromethyl)phenyl ether		C₁₆H₁₄ClF₃O	详情	详情

合成路线3

该中间体在本合成路线中的序号：(II)

Reduction of 3-chloropropiophenone (I) with NaBH4 produced 3-chloro-1-phenyl-1-propanol (II). Subsequent Mitsunobu coupling of (II) with 2-(methylthio)phenol (III) in the presence of DEAD and PPh3 afforded ether (IV). Finally, substitution of the halogen of (IV) for methylamine provided the corresponding secondary amine.

参考文献中间体

合成目标

【1】 Gehlert, D.R.; Robertson, D.W.; Wong, D.T. (Eli Lilly and Company); N-Alkyl-3-phenyl-3-(2-alkylthiophenoxy)propylamines. EP 0591581 .

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
	11021	Methanamine; Methylamine	74-89-5	CH₅N	详情	详情
(I)	28073	3-chloro-1-phenyl-1-propanone	936-59-4	C₉H₉ClO	详情	详情
(II)	28074	3-chloro-1-phenyl-1-propanol		C₉H₁₁ClO	详情	详情
(III)	28075	2-(methylsulfanyl)phenol	1073-29-6	C₇H₈OS	详情	详情
(IV)	28076	1-(3-chloro-1-phenylpropoxy)-2-(methylsulfanyl)benzene		C₁₆H₁₇ClOS	详情	详情

合成路线4

该中间体在本合成路线中的序号：(II)

The reduction of omega-chloropropiophenone (I) with NaBH4 in ethanol gives 3-chloro-1-phenyl-1-propanol (II), which is treated with butyric anhydride and pyridine in dichloromethane yielding the corresponding racemic ester (III). The optical resolution of (III) with immobilized lipase B from Candida antarctica (CALB) affords a mixture of unreacted (S)-ester and (R)-alcohol (IV) that are separated by column chromatography. The condensation of alcohol (IV) with 2-methoxyphenol (V) by means of PPh3 and diethyl azodicarboxylate (DEAD) in THF gives the corresponding ether (VI), which is finally treated with methylamine in refluxing ethanol.

参考文献中间体

合成目标

【1】 Anthonsen, T.; Ho, B.H.; Liu, H.L.; Chemoenzymatic synthesis of the non-tricyclic antidepressants fluoxetine, tomoxetine and nisoxetine. J Chem Soc - Perkins Trans I 2000, 11, 11, 1767.

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
	11021	Methanamine; Methylamine	74-89-5	CH₅N	详情	详情
(I)	28073	3-chloro-1-phenyl-1-propanone	936-59-4	C₉H₉ClO	详情	详情
(II)	28074	3-chloro-1-phenyl-1-propanol		C₉H₁₁ClO	详情	详情
(III)	37781	3-chloro-1-phenylpropyl butyrate		C₁₃H₁₇ClO₂	详情	详情
(IV)	37782	(1R)-3-chloro-1-phenyl-1-propanol		C₉H₁₁ClO	详情	详情
(V)	13182	Guaiacol; 2-Methoxyphenol	90-05-1	C₇H₈O₂	详情	详情
(VI)	37783	1-[[(1R)-3-chloro-1-phenylpropyl]oxy]-2-methoxybenzene; (1R)-3-chloro-1-phenylpropyl 2-methoxyphenyl ether		C₁₆H₁₇ClO₂	详情	详情

Extended Information