2-Hydroxy-4-methylbenzoic acid; 2-Hydroxy-p-toluic Acid; 4-Methylsalicylic acid; m-Cresotinic acid -Drug Synthesis Database

【结构式】

【分子编号】53446

【品名】2-Hydroxy-4-methylbenzoic acid; 2-Hydroxy-p-toluic Acid; 4-Methylsalicylic acid; m-Cresotinic acid

【CA登记号】50-85-1

【分子式】C₈H₈O₃

【分子量】152.14972

【元素组成】C 63.15% H 5.3% O 31.55%

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 2-hydroxy-4-methylbenzoic acid (I) with ethyl bromide (II) and K2CO3 in acetone at 150 C gives 2-ethoxy-4-methylbenzoic acid ethyl ester (III), which is brominated with Br2 and AIBN in CCl4 to yield the bromomethyl derivative (IV). The reaction of (IV) with NaCN and benzyl-tributylammonium chloride affords the cyanomethyl compound (V), which is hydrolyzed with HCl (g) in refluxing ethanol to provide 2-ethoxy-4-(ethoxycarbonylmethyl)benzoic acid ethyl ester (VI). Finally, this compound is selectively hydrolyzed with 2N NaOH in ethanol to furnish the target intermediate, the 2-[3-ethoxy-4-(ethoxycarbonyl)phenyl]acetic acid (VII).

参考文献中间体

合成目标

【1】 Salman, M.; et al.; An efficient and cost-effective synthesis of 3-ethoxy-4-ethoxycarbonyl-phenylacetic acid: A key acid synthon of repaglinide. Org Process Res Dev 2002, 6, 2, 184.
【2】 Grell, W.; Hurnaus, R.; Griss, G.; Sauter, R.; Rupprecht, E.; Mark, M.; Luger, P.; Nar, H.; Wittneben, H.; Muller, P.; Repaglinide and related hypoglycemic benzoic acid derivatives. J Med Chem 1998, 41, 26, 5219.

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)	53446	2-Hydroxy-4-methylbenzoic acid; 2-Hydroxy-p-toluic Acid; 4-Methylsalicylic acid; m-Cresotinic acid	50-85-1	C₈H₈O₃	详情	详情
(II)	19502	Propyl bromide; 1-Bromopropane	106-94-5	C₃H₇Br	详情	详情
(III)	53447	ethyl 2-ethoxy-4-methylbenzoate	88709-17-5	C₁₂H₁₆O₃	详情	详情
(IV)	53448	ethyl 4-(bromomethyl)-2-ethoxybenzoate	n/a	C₁₂H₁₅BrO₃	详情	详情
(V)	53449	ethyl 4-(cyanomethyl)-2-ethoxybenzoate	n/a	C₁₃H₁₅NO₃	详情	详情
(VI)	53450	ethyl 2-ethoxy-4-(2-ethoxy-2-oxoethyl)benzoate	n/a	C₁₅H₂₀O₅	详情	详情
(VII)	15301	2-[3-ethoxy-4-(ethoxycarbonyl)phenyl]acetic acid		C₁₃H₁₆O₅	详情	详情

合成路线2

该中间体在本合成路线中的序号：(I)

The reaction of 2-hydroxy-4-methylbenzoic acid (I) with ethyl bromide (II) and K2CO3 in DMSO gives 2-ethoxy-4-methylbenzoic acid ethyl ester (III), which is carboxylated by reaction with LDA and CO2 in THF/1,3-dimethylperhydropyrimidin-2-one to furnish the target intermediate the 2-[3-ethoxy-4-(ethoxycarbonyl)phenyl]acetic acid (IV).

参考文献中间体

合成目标

【1】 Salman, M.; et al.; An efficient and cost-effective synthesis of 3-ethoxy-4-ethoxycarbonyl-phenylacetic acid: A key acid synthon of repaglinide. Org Process Res Dev 2002, 6, 2, 184.
【2】 Kumar, N.; Biswas, S.; Salman, M.; Babu, S.J.; Ray, P.C. (Ranbaxy Laboratories Ltd.); Synthesis of 3-ethoxy-4-ethoxycarbonyl phenyl acetic acid, a key acid synthon of repaglinide. WO 0135900 .

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)	53446	2-Hydroxy-4-methylbenzoic acid; 2-Hydroxy-p-toluic Acid; 4-Methylsalicylic acid; m-Cresotinic acid	50-85-1	C₈H₈O₃	详情	详情
(II)	19502	Propyl bromide; 1-Bromopropane	106-94-5	C₃H₇Br	详情	详情
(III)	53447	ethyl 2-ethoxy-4-methylbenzoate	88709-17-5	C₁₂H₁₆O₃	详情	详情
(IV)	15301	2-[3-ethoxy-4-(ethoxycarbonyl)phenyl]acetic acid		C₁₃H₁₆O₅	详情	详情

Extended Information