3-[(4-phenoxyphenyl)sulfonyl]-1-propanol -Drug Synthesis Database

【结构式】

【分子编号】27078

【品名】3-[(4-phenoxyphenyl)sulfonyl]-1-propanol

【CA登记号】

【分子式】C₁₅H₁₆O₄S

【分子量】292.35564

【元素组成】C 61.63% H 5.52% O 21.89% S 10.97%

与该中间体有关的原料药合成路线共 3 条

合成路线1 合成路线2 合成路线3

合成路线1

该中间体在本合成路线中的序号：(V)

Alkylation of 4-fluorothiophenol (I) with 3-chloropropanol (II) in the presence of K2CO3 in DMF provided thioether (III), which was oxidized to sulfone (IV) using Oxone(R). Fluorine displacement in (IV) with phenol and K2CO3 gave phenoxy derivative (V). Subsequent Mitsunobu condensation of (V) with thioacetic acid afforded thioacetate ester (VI), which by further hydrolysis with NaOMe furnished the target thiol.

参考文献中间体

合成目标

【1】 Freskos, J.N.; Abbas, Z.S.; Decrescenzo, G.A.; Getman, D.P.; Heintz, R.M.; Mischke, B.V.; McDonald, J.J. (Pharmacia Corp.); Thiol sulfone metalloprotease inhibitors. EP 0939628; WO 9803164 .

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
	23540	Phenol	108-95-2	C₆H₆O	详情	详情
(I)	22971	4-fluorobenzenethiol; 4-fluorophenylhydrosulfide; 4-Fluorothiophenol	371-42-6	C₆H₅FS	详情	详情
(II)	19490	3-chloro-1-propanol	627-30-5	C₃H₇ClO	详情	详情
(III)	27076	3-[(4-fluorophenyl)sulfanyl]-1-propanol		C₉H₁₁FOS	详情	详情
(IV)	27077	3-[(4-fluorophenyl)sulfonyl]-1-propanol		C₉H₁₁FO₃S	详情	详情
(V)	27078	3-[(4-phenoxyphenyl)sulfonyl]-1-propanol		C₁₅H₁₆O₄S	详情	详情
(VI)	27079	S-[3-[(4-phenoxyphenyl)sulfonyl]propyl] ethanethioate		C₁₇H₁₈O₄S₂	详情	详情

合成路线2

该中间体在本合成路线中的序号：(V)

The intermediate sulfone alcohol (V) has been obtained by an alternative procedure. 4-Phenoxyphenol (VII) was converted to thiophenol (IX) through the sequence of condensation with N,N-dimethylthiocarbamyl chloride, followed by thermal rearrangement of the resulting O-aryl thiocarbamate (VIII) to the S-aryl thiocarbamate, and then hydrolysis with KOH. Alkylation with 3-chloropropanol (II) provided thioether (X), which was then oxidized to the sulfone (V) with Oxone(R).

参考文献中间体

合成目标

【1】 Inturrisi, C.E.; Collins, J.J.; Dunkel, I.J.; Portenoy, R.K.; Palmer, L.N.; Lapin, J.; Gupta, S.K.; Weinstein, S.M.; Transdermal fentanyl in children with cancer pain: Feasibility, tolerability, and pharmacokinetic correlates. J Pediatr 1999, 134, 3, 319.

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(II)	19490	3-chloro-1-propanol	627-30-5	C₃H₇ClO	详情	详情
(V)	27078	3-[(4-phenoxyphenyl)sulfonyl]-1-propanol		C₁₅H₁₆O₄S	详情	详情
(VII)	27080	4-Phenoxyphenol	831-82-3	C₁₂H₁₀O₂	详情	详情
(VIII)	27081	O-(4-phenoxyphenyl) dimethylcarbamothioate		C₁₅H₁₅NO₂S	详情	详情
(IX)	26254	4-phenoxybenzenethiol; 4-phenoxyphenylhydrosulfide		C₁₂H₁₀OS	详情	详情
(X)	27082	3-[(4-phenoxyphenyl)sulfanyl]-1-propanol		C₁₅H₁₆O₂S	详情	详情

合成路线3

该中间体在本合成路线中的序号：(V)

Alkylation of 4-fluorothiophenol (I) with 3-chloropropanol (II) in the presence of K2CO3 in DMF provided thioether (III), which was oxidized to sulfone (IV) using Oxone(R). Fluorine displacement in (IV) with thiophenol and K2CO3 gave phenylsulfanyl derivative (V). The hydroxyl group of (V) was converted to mesylate (VI) and then displaced by potassium thioacetate to afford thioacetate ester (VII). Finally, hydrolysis with methanolic NaOMe furnished the target thiol.

参考文献中间体

合成目标

【1】 Inturrisi, C.E.; Collins, J.J.; Dunkel, I.J.; Portenoy, R.K.; Palmer, L.N.; Lapin, J.; Gupta, S.K.; Weinstein, S.M.; Transdermal fentanyl in children with cancer pain: Feasibility, tolerability, and pharmacokinetic correlates. J Pediatr 1999, 134, 3, 319.
【2】 Freskos, J.N.; Abbas, Z.S.; Decrescenzo, G.A.; Getman, D.P.; Heintz, R.M.; Mischke, B.V.; McDonald, J.J. (Pharmacia Corp.); Thiol sulfone metalloprotease inhibitors. EP 0939628; WO 9803164 .

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
	12951	Benzenethiol; Phenylmercaptan; Phenylhydrosulfide	108-98-5	C₆H₆S	详情	详情
(I)	22971	4-fluorobenzenethiol; 4-fluorophenylhydrosulfide; 4-Fluorothiophenol	371-42-6	C₆H₅FS	详情	详情
(II)	19490	3-chloro-1-propanol	627-30-5	C₃H₇ClO	详情	详情
(III)	27076	3-[(4-fluorophenyl)sulfanyl]-1-propanol		C₉H₁₁FOS	详情	详情
(IV)	27077	3-[(4-fluorophenyl)sulfonyl]-1-propanol		C₉H₁₁FO₃S	详情	详情
(V)	27078	3-[(4-phenoxyphenyl)sulfonyl]-1-propanol		C₁₅H₁₆O₄S	详情	详情
(VI)	27083	3-[[4-(phenylsulfanyl)phenyl]sulfonyl]propyl methanesulfonate		C₁₆H₁₈O₅S₃	详情	详情
(VII)	27084	S-(3-[[4-(phenylsulfanyl)phenyl]sulfonyl]propyl) ethanethioate		C₁₇H₁₈O₃S₃	详情	详情

Extended Information