• Archives of Pharmacal Research
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• 제17권1호
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• pp.17-20
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• 1994

Friedel-Crafts reaction of fluorene with methyl ${\alpha}$-chloro-${\alpha}$-(methylthio)acetate 1 gave methyl $\alpha$-methylthio-2-fluoreneacetate 2. Cicloprofen 8, a potent antiinflammatory agent, was prepared by methylation of 2 followed by reductive desulfurization of methyl 2(2-fluorenyl)-2-(methylthio)propionate 6 and hydrolysis of methyl 2-(2-fluorenyl)propionate 7.

• Archives of Pharmacal Research
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• 제15권2호
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• pp.142-145
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• 1992

A novel preparative method for hexaprofen, which is a potent antiinflammatory agent, is described. Friedel-Crafts reaction of cyclohexylbenzene with ethyl $\alpha$-chloro-$\alpha$-(methylthio) acetate 1 and $\alpha$-chloro-$\alpha$-(methylthio) acetonitrile 2 afforded ethyl 2-(methylthio)-2-(4-cyclohexylphenyl) acetate 7 and 2-methylthio-2-(4-cyclohexylphenyl) acetonitrile 8, respectively. Compounds 7 and 8 were converted into the corresponding ethyl 2-methylthio-2-(4-cyclohexylphenyl) propionate 9 and 2-methylthio-2-(4-cyclohexylphenyl) propionitrile 10 by methylation with sodium hydride and methyl iodide. Hexaprofen 13 was prepard by hydrolysis of ethyl 2-(4-cyclohexylphenyl) propionate 11 and of 2-(4-cyclohexylphenyl) propionitrile 12 followed by desulfurization of compounds 9 and 10.

• Archives of Pharmacal Research
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• 제16권4호
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• pp.343-346
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• 1993

A new method was described for the preparation of 7-[p-(methylthio)benzoyl]-5-benzofuranacetic acid 6, which is an analgestic agent. Methyl 5-(2, 3-di-hydobenzofuran)acetate 3 was obtained by Friedel-Crafts reaction of 2, 3-dihydrobenzofuran with methyl .alpha.-chloro-.alpha.(methylthio)actate 1 and desulfurization of 2. Tifurac 6 was synthesized from acylation of 3 with p-(methythio)benzoyl chioride followed by bromination of 4, dehydrohalogenation, and hydrolysis of 5.

• 약학회지
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• 제33권4호
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• pp.237-240
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• 1989

A new synthetic method for tiaprofenic acid, which is a potent anti-inflammatory agent, was described. Friedel-Crafts reaction of thiophene with ethyl ${\alpha}-chloro-{\alpha}-(methylthio)$ acetate (1) gave ethyl ${\alpha}-methylthio-2-thiopheneacetate$ (3). Ethyl ${\alpha}-methyl-2-thiopheneacetate$ (5) was prepared by treatment of (3) with NaH and MeI, followed by desulfurization with zinc dust-acetic acid of the resultant ethyl ${\alpha}-methyl-{\alpha}-methylthio-2-thiopheneacetate$ (4). Tiaprofenic acid (7) could be easily synthesized by benzoylation of (5) and hydrolysis of the resultant ethyl $5-benzoyl-{\alpha}-methyl-2-thiopheneacetate$ (6).

• 약학회지
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• 제41권4호
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• pp.480-483
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• 1997

The efficient synthesis of p-(acetylamino)phenylacetic acid(7), a antirheumatic agent, is reported. Methyl phenylacetate(3) was prepared from Friedel- Crafts reaction of benzene with methyl ${\alpha}$-chloro-${\alpha}$-(methylthio)acetate(1) followed by reductive desulfurization with zinc dust in acetic acid. Compound(7) was obtained from 3 by a sequence of nitration, reduction, N-acylation, and hydrolysis.

• 약학회지
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• 제36권4호
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• pp.341-344
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• 1992

A facile method for tolmetin, which is a potent antiinflammatory agent, is described. Friedel-Crafts reaction of 1-methylpyrrole with ethyl ${\alpha}-chloro-{\alpha}-(methylthio)acetate$ (1) gave ethyl ${\alpha}-methylthio$-1-methyl-2-pyrroleacetate (4), which was readily converted into ethyl 1-methyl-2-pyrroleacetate (5) by reductive desulfurization with zinc dust in acetic acid. Tolmetin was synthesized by Friedel-Crafts acylation of (5) with p-toluoyl chloride, followed by hydrolysis of the resultant ethyl 5-(p-toluoyl)-1-methylpyrrole-2-acetate (6).

• 약학회지
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• 제38권5호
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• pp.504-510
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• 1994

A facile synthesis of 2-aryl-5-benzoxazolepropionic acid derivatives(1 0a-d), which are potent antiinflammatory agent, is reported. Methyl ${\alpha}$-(p-hydroxyphenyl)propionate(5) was prepared from Friedel-Crafts reaction of isopropoxy benzene with methyl ${\alpha}$-chloro-${\alpha}$-(methylthio) acetate(1), followed by desulfurization, methylation and clevage of ether bond. Compounds(10a-d) were made from(5) by a sequence of nitration, reduction, formation of benzoxazole ring, and hydrolysis in good yields, respectively.

• Archives of Pharmacal Research
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• 제17권3호
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• pp.190-193
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• 1994

Friedel-Crafts reaction isopropoxybenzene with methyl $\alpha$-chloro-$\alpha$-(maethylthio)acetate 1 afforded methyl $\alpha$-methylthio-p-isopropoxyphenylacetate 2d, which was readily converted into methyl p-isopropoxyphenylacetate 3 by reductive desulfurization with zinc dust in acetic acid. Methylation of 3 with sodium hydride and methyl iodide gave methyl $\alpha$-(p-isopropoxyphenyl)propionate 5. Methyl p-hydroxyphenylakanoates (4,6), useful intermediates for some medicines, were easily prepared by treatment of 3 and 5 with titanium tetrachloride, respectively.

• Archives of Pharmacal Research
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• 제19권2호
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• pp.148-152
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• 1996

The efficient synthesis of 4-(2-thiazolyloxy)phenylalkanoic acids (10a-c), which are a potent antiinflammatory agent, was achieved in 5-6 steps starting from isopropoxybenzene and methyl $\alpha-chloro-\alpha-(methylthio)acetate (1)$. The key intermediate (4) was prepared by Friedel-Crafts reaction of isopropoxybenzene with (1) followed by desulfurization and the removal of isopropyl protector. Methyl 4-hydroxyphenylalkanoates (6, 8) were similarly obtained from alkylation of (3) and deprotection.