methyl 2-(2-methyl-4-sulfanylphenoxy)acetate -Drug Synthesis Database

【结构式】

【分子编号】49899

【品名】methyl 2-(2-methyl-4-sulfanylphenoxy)acetate

【CA登记号】

【分子式】C₁₀H₁₂O₃S

【分子量】212.26948

【元素组成】C 56.58% H 5.7% O 22.61% S 15.11%

与该中间体有关的原料药合成路线共 2 条

合成路线1 合成路线2

合成路线1

该中间体在本合成路线中的序号：(VII)

Alkylation of 4'-hydroxy-3'-methylacetophenone (I) with methyl bromoacetate in the presence of Cs2CO3 afforded the aryloxyacetate (II). Baeyer-Villiger rearrangement of the acetophenone moiety using meta-chloroperbenzoic acid produced the aryl ester (III), which was further converted to phenol (IV) by transesterification with methanolic NaOMe. Reaction of (IV) with dimethylthiocarbamoyl chloride gave the O-aryl thiocarbamate (V), which was thermally rearranged to the S-aryl thiocarbamate (VI) in refluxing tetradecane. Then, basic hydrolysis of the thiocarbamate function provided the thiophenol (VII). Alternatively, thiophenol (VII) was obtained by chlorosulfonation of ethyl (2-methylphenoxy)acetate (VIII), followed by reduction of the resultant sulfonyl chloride (IX) with Sn and HCl.

参考文献中间体

合成目标

【1】 Maloney, P.R.; Gellibert, F.J.; Sierra, M.L.; Chao, E.Y.-H.; Haffner, C.D.; Willson, T.M.; Sznaidman, M.L.; Xu H.E.; Lambert, M.H. III; Sternbach, D.D. (Glaxo Group Ltd.); Thiazole and oxazole derivs. and their pharmaceutical use. WO 0100603 .

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)	49893	2-Methyl-4-acetophenol; 4-Hydroxy-3-methylacetophenone	876-02-8	C₉H₁₀O₂	详情	详情
(II)	49894	methyl 2-(4-acetyl-2-methylphenoxy)acetate		C₁₂H₁₄O₄	详情	详情
(III)	49895	methyl 2-[4-(acetoxy)-2-methylphenoxy]acetate		C₁₂H₁₄O₅	详情	详情
(IV)	49896	methyl 2-(4-hydroxy-2-methylphenoxy)acetate		C₁₀H₁₂O₄	详情	详情
(V)	49897	methyl 2-(4-[[(dimethylamino)carbothioyl]oxy]-2-methylphenoxy)acetate		C₁₃H₁₇NO₄S	详情	详情
(VI)	49898	methyl 2-(4-[[(dimethylamino)carbonyl]sulfanyl]-2-methylphenoxy)acetate		C₁₃H₁₇NO₄S	详情	详情
(VII)	49899	methyl 2-(2-methyl-4-sulfanylphenoxy)acetate		C₁₀H₁₂O₃S	详情	详情
(VIII)	49900	methyl 2-(2-methylphenoxy)acetate		C₁₀H₁₂O₃	详情	详情
(IX)	49901	methyl 2-[4-(chlorosulfonyl)-2-methylphenoxy]acetate		C₁₀H₁₁ClO₅S	详情	详情

合成路线2

该中间体在本合成路线中的序号：(VII)

4-Trifluoromethylbenzamide (X) was converted to the corresponding thioamide (XI) by treatment with P4S10. Condensation of (XI) with ethyl 2-chloroacetoacetate (XII) provided thiazole (XIII). Subsequent reduction of the ester group of (XIII) with LiAlH4 gave alcohol (XIV). Conversion of (XIV) to the corresponding chloride (XV) was carried out by reaction with methanesulfonyl chloride and triethylamine. Chloride (XV) was then condensed with thiophenol (VII) in the presence of Cs2CO3 to yield thioether (XVI). The methyl ester group was finally hydrolyzed to the title acid employing LiOH.

参考文献中间体

合成目标

【1】 Maloney, P.R.; Gellibert, F.J.; Sierra, M.L.; Chao, E.Y.-H.; Haffner, C.D.; Willson, T.M.; Sznaidman, M.L.; Xu H.E.; Lambert, M.H. III; Sternbach, D.D. (Glaxo Group Ltd.); Thiazole and oxazole derivs. and their pharmaceutical use. WO 0100603 .

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(VII)	49899	methyl 2-(2-methyl-4-sulfanylphenoxy)acetate		C₁₀H₁₂O₃S	详情	详情
(X)	49902	alpha,alpha,alpha-Trifluoro-p-toluamide; 4-Trifluoromethylbenzamide	1891-90-3	C₈H₆F₃NO	详情	详情
(XI)	49903	4-(Trifluoromethyl)thiobenzamide	72505-21-6	C₈H₆F₃NS	详情	详情
(XII)	21337	ethyl 2-chloro-3-oxobutanoate	609-15-4	C₆H₉ClO₃	详情	详情
(XIII)	49904	Ethyl 4-methyl-2-[4-(trifluoromethyl)phenyl]-thiazole-5-carboxylate	175277-03-9	C₁₄H₁₂F₃NO₂S	详情	详情
(XIV)	49905	[4-methyl-2-[4-(trifluoromethyl)phenyl]-1,3-thiazol-5-yl]methanol		C₁₂H₁₀F₃NOS	详情	详情
(XV)	49906	5-(chloromethyl)-4-methyl-2-[4-(trifluoromethyl)phenyl]-1,3-thiazole		C₁₂H₉ClF₃NS	详情	详情
(XVI)	49907	methyl 2-[2-methyl-4-[([4-methyl-2-[4-(trifluoromethyl)phenyl]-1,3-thiazol-5-yl]methyl)sulfanyl]phenoxy]acetate		C₂₂H₂₀F₃NO₃S₂	详情	详情

Extended Information