methyl 5-acetyl-2-hydroxybenzoate -Drug Synthesis Database

【结构式】

【分子编号】30753

【品名】methyl 5-acetyl-2-hydroxybenzoate

【CA登记号】16475-90-4

【分子式】C₁₀H₁₀O₄

【分子量】194.187

【元素组成】C 61.85% H 5.19% O 32.96%

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：(I)

The reaction of methyl-5-acetylsalicylate (I) with alpha-bromo-gamma-butyrolactone (II) by means of K2CO3 in refluxing acetone gives alpha-[(2-methoxycarbonyl-4-acetylphenyl)oxy]-gamma-butyrolactone (III), which is hydrolyzed with NaOH in methanol yielding alpha-[(2-carboxy-4-acetylphenyl)oxy]-gamma-butyrolactone (IV). The cyclization of (IV) with refluxing acetic anhydride affords 5-acetyl-4',5'-dihydrospiro[benzofuran-2(3H),3'(2'H)-furan]-2',3-dione (V), which is finally treated at 155 C in dimethylsulfoxide containing NaCl.

参考文献中间体

合成目标

【1】 Hirosada, S.; Watanabe, M.; Mitsuru, K.; Isuke, I. (Takeda Chemical Industries, Ltd.); Spirobenzofuranone compounds, processes for their preparation and their use as medicines. CA 1113467; DE 2861651; EP 0003084; ES 476330; ES 8102114; JP 54098752; ZA 7807296 .
【2】 Blancafort, P.; Castaner, J.; Serradell, M.N.; AG-629. Drugs Fut 1983, 8, 2, 92.

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)	30753	methyl 5-acetyl-2-hydroxybenzoate	16475-90-4	C₁₀H₁₀O₄	详情	详情
(II)	22822	3-bromodihydro-2(3H)-furanone	5061-21-2	C₄H₅BrO₂	详情	详情
(III)	30754	methyl 5-acetyl-2-[(2-oxotetrahydro-3-furanyl)oxy]benzoate		C₁₄H₁₄O₆	详情	详情
(IV)	30755	5-acetyl-2-[(2-oxotetrahydro-3-furanyl)oxy]benzoic acid		C₁₃H₁₂O₆	详情	详情
(V)	30756	5-Acetyl-2,2',3,3',4',5'-hexahydrospiro[benzofuran-2,2'-furan]-3,3'-dione		C₁₃H₁₀O₅	详情	详情

合成路线2

该中间体在本合成路线中的序号：(III)

The Friedel-Crafts condensation of 2-hydroxybenzoic acid methyl ester (I) with 13C-labeled acetyl chloride (II) by means of AlCl3 in dichloromethane gives 5-acetyl-2-hydroxybenzoic acid methyl ester (III), which is brominated with Br2 in CHCl3 yielding the bromoacetyl compound (IV). The condensation of (IV) with the secondary amine (V) by means of DIEA in THF affords the tertiary amine (VI), which is reduced with LiAlD4 in refluxing ethyl ether to provide the trideuterated triol (VII). Finally, this compound is debenzylated by hydrogenation with H2 over Pd/C in ethanol.

参考文献中间体

合成目标

【1】 Goodwin, T.E.; et al.; Synthesis of 13C,2H3-salmeterol: An analytical internal standard for pharmacokinetic studies. J Label Compd Radiopharm 2000, 43, 1, 65.

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)	15754	methyl salicylate	119-36-8	C₈H₈O₃	详情	详情
(II)	19273	acetyl chloride	75-36-5	C₂H₃ClO	详情	详情
(II)	44648	acetyl chloride	1520-57-6	C₂H₃ClO	详情	详情
(III)	30753	methyl 5-acetyl-2-hydroxybenzoate	16475-90-4	C₁₀H₁₀O₄	详情	详情
(III)	44649	methyl 5-acetyl-2-hydroxybenzoate		C₁₀H₁₀O₄	详情	详情
(IV)	35836	methyl 5-(2-bromoacetyl)-2-hydroxybenzoate		C₁₀H₉BrO₄	详情	详情
(IV)	44650	methyl 5-(2-bromoacetyl)-2-hydroxybenzoate		C₁₀H₉BrO₄	详情	详情
(V)	35837	N-benzyl-6-(4-phenylbutoxy)-1-hexanamine; N-benzyl-N-[6-(4-phenylbutoxy)hexyl]amine		C₂₃H₃₃NO	详情	详情
(VI)	35838	methyl 5-(2-[benzyl[6-(4-phenylbutoxy)hexyl]amino]acetyl)-2-hydroxybenzoate		C₃₃H₄₁NO₅	详情	详情
(VI)	44651	methyl 5-(2-[benzyl[6-(4-phenylbutoxy)hexyl]amino]acetyl)-2-hydroxybenzoate		C₃₃H₄₁NO₅	详情	详情
(VII)	35839	4-(2-[benzyl[6-(4-phenylbutoxy)hexyl]amino]-1-hydroxyethyl)-2-(hydroxymethyl)phenol		C₃₂H₄₃NO₄	详情	详情
(VII)	44652	4-(2-[benzyl[6-(4-phenylbutoxy)hexyl]amino]-1-hydroxyethyl)-2-(hydroxymethyl)phenol		C₃₂H₄₃NO₄	详情	详情

Extended Information