|
【结 构 式】 
|
【分子编号】62687 【品名】2-[4-(3-methyl-2-thienyl)phenyl]propanoic acid 【CA登记号】 |
【 分 子 式 】C14H14O2S 【 分 子 量 】246.32996 【元素组成】C 68.26% H 5.73% O 12.99% S 13.02% |
合成路线1
该中间体在本合成路线中的序号：(IX)The Darzen's condensation of 4-iodoacetophenone (I) with methyl chloroacetate (II) in the presence of NaOMe afforded the glycidic ester (III), which was further hydrolyzed to the corresponding glycidic acid (IV) with NaOH in aqueous ethanol. Subsequent decarboxylation of (IV) under acidic conditions furnished 2-(4-iodophenyl)propionaldehyde (V). After oxidation of aldehyde (V) with sodium chlorite, the resultant carboxylic acid was converted to the corresponding zinc salt (VI) upon treatment with ZnCl2 and NaOH. Coupling of aryl iodide (VI) with the Grignard reagent (VIII) (prepared from 2-bromo-3-methylthiophene (VII)) in the presence of PdCl2 gave rise to the racemic biarylpropionic acid (IX)). The title (R)-enantiomer was then resolved via formation of the diastereoisomeric salts with D-phenylglycine methyl ester (X)
| 【2】 Arai, H.; Tanaka, K.; Watanabe, I.; Kodama, T.; Hirano, H.; Abe, N.; Nakabayashi, M. (Toyama Chemical Co., Ltd.); Novel 2-[4-(3-methyl-2-thienyl)phenyl]propionic acid and pharmaceutically acceptable salt thereof and method for treating symptoms of inflammation and pain. US 4230719 . |
| 【1】 Kodama, T.; Nakabayashi, M.; Watanabe, I.; Hirano, Y.; Abe, N.; Tanaka, K.; Arai, H. (Toyama Chemical Co., Ltd.); 2-[4-(3-Methyl-2-thienyl)phenyl]propionic acid derivs. and its non-toxic salts. DE 2850485; JP 1981049376 . |
| 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) | 51497 | 4'-Iodoacetophenone; 4-Iodoacetophenone; 1-(4-Iodophenyl)ethanone | 13329-40-3 | C8H7IO | 详情 | 详情 |
| (II) | 10257 | methyl 2-chloroacetate; methyl chloroacetate | 96-34-4 | C3H5ClO2 | 详情 | 详情 |
| (III) | 62683 | methyl 3-(4-iodophenyl)-3-methyl-2-oxiranecarboxylate | C11H11IO3 | 详情 | 详情 | |
| (IV) | 62684 | 3-(4-iodophenyl)-3-methyl-2-oxiranecarboxylic acid | C10H9IO3 | 详情 | 详情 | |
| (V) | 62685 | 2-(4-iodophenyl)propanal | C9H9IO | 详情 | 详情 | |
| (VI) | 62686 | C18H16I2O4Zn | 详情 | 详情 | ||
| (VII) | 12443 | 2-Bromo-3-methylthiophene | 14282-76-9 | C5H5BrS | 详情 | 详情 |
| (VIII) | 36973 | bromo(3-methyl-2-thienyl)magnesium | C5H5BrMgS | 详情 | 详情 | |
| (IX) | 62687 | 2-[4-(3-methyl-2-thienyl)phenyl]propanoic acid | C14H14O2S | 详情 | 详情 | |
| (X) | 10717 | methyl (2S)-2-amino-2-phenylethanoate | C9H11NO2 | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(IX)Preparation of the racemic arylpropionic acid (IX) has been reported through a number of different procedures. 4-Aminoacetophenone (XI) was diazotized to (XII) employing isoamyl nitrite and either acetic or fluoboric acid. Then, the Gomberg-Bachmann coupling of diazonium salt (XII) with 3-methylthiophene (XIII) furnished 4-(3-methyl-2-thienyl)acetophenone (XIV). Subsequent Darzen's condensation of acetophenone (XIV) with methyl chloroacetate (II) afforded the glycidic ester (XV), which was further hydrolyzed to acid (XVI), and then decarboxylated to aldehyde (XVII). Oxidation of (XVII) to the key carboxylic acid was performed by treatment with potassium permanganate
| 【2】 Arai, H.; Tanaka, K.; Watanabe, I.; Kodama, T.; Hirano, H.; Abe, N.; Nakabayashi, M. (Toyama Chemical Co., Ltd.); Novel 2-[4-(3-methyl-2-thienyl)phenyl]propionic acid and pharmaceutically acceptable salt thereof and method for treating symptoms of inflammation and pain. US 4230719 . |
| 【1】 Kodama, T.; Nakabayashi, M.; Watanabe, I.; Hirano, Y.; Abe, N.; Tanaka, K.; Arai, H. (Toyama Chemical Co., Ltd.); 2-[4-(3-Methyl-2-thienyl)phenyl]propionic acid derivs. and its non-toxic salts. DE 2850485; JP 1981049376 . |
| 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) | 10257 | methyl 2-chloroacetate; methyl chloroacetate | 96-34-4 | C3H5ClO2 | 详情 | 详情 |
| (IX) | 62687 | 2-[4-(3-methyl-2-thienyl)phenyl]propanoic acid | C14H14O2S | 详情 | 详情 | |
| (XI) | 27847 | 1-(4-aminophenyl)-1-ethanone | 99-92-3 | C8H9NO | 详情 | 详情 |
| (XII) | 62688 | 4-acetylbenzenediazonium | C8H7N2O | 详情 | 详情 | |
| (XIII) | 12442 | 3-Methylthiophene | 616-44-4 | C5H6S | 详情 | 详情 |
| (XIV) | 62689 | 1-[4-(3-methyl-2-thienyl)phenyl]-1-ethanone | C13H12OS | 详情 | 详情 | |
| (XV) | 62690 | methyl 3-methyl-3-[4-(3-methyl-2-thienyl)phenyl]-2-oxiranecarboxylate | C16H16O3S | 详情 | 详情 | |
| (XVI) | 62691 | 3-methyl-3-[4-(3-methyl-2-thienyl)phenyl]-2-oxiranecarboxylic acid | C15H14O3S | 详情 | 详情 | |
| (XVII) | 62692 | 2-[4-(3-methyl-2-thienyl)phenyl]propanal | C14H14OS | 详情 | 详情 |
合成路线3
该中间体在本合成路线中的序号：(IX)Alternatively, Darzen's condensation of acetophenone (XIV) with methyl 2-chloropropionate (XVIII) produced glycidic ester (XIX), which was hydrolyzed and decarboxylated to the 3-arylbutanone (XX). The haloform reaction of ketone (XX) with sodium hypobromite generated acid (IX)
| 【2】 Arai, H.; Tanaka, K.; Watanabe, I.; Kodama, T.; Hirano, H.; Abe, N.; Nakabayashi, M. (Toyama Chemical Co., Ltd.); Novel 2-[4-(3-methyl-2-thienyl)phenyl]propionic acid and pharmaceutically acceptable salt thereof and method for treating symptoms of inflammation and pain. US 4230719 . |
| 【1】 Kodama, T.; Nakabayashi, M.; Watanabe, I.; Hirano, Y.; Abe, N.; Tanaka, K.; Arai, H. (Toyama Chemical Co., Ltd.); 2-[4-(3-Methyl-2-thienyl)phenyl]propionic acid derivs. and its non-toxic salts. DE 2850485; JP 1981049376 . |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (IX) | 62687 | 2-[4-(3-methyl-2-thienyl)phenyl]propanoic acid | C14H14O2S | 详情 | 详情 | |
| (XIV) | 62689 | 1-[4-(3-methyl-2-thienyl)phenyl]-1-ethanone | C13H12OS | 详情 | 详情 | |
| (XVIII) | 35742 | methyl (2S)-2-chloropropanoate | C4H7ClO2 | 详情 | 详情 | |
| (XIX) | 62693 | methyl 2,3-dimethyl-3-[4-(3-methyl-2-thienyl)phenyl]-2-oxiranecarboxylate | C17H18O3S | 详情 | 详情 | |
| (XX) | 62694 | 3-[4-(3-methyl-2-thienyl)phenyl]-2-butanone | C15H16OS | 详情 | 详情 |
合成路线4
该中间体在本合成路线中的序号：(IX)Acetophenone (XIV) was converted to oxirane (XXI) by treatment with the in situ-generated dimethylsulfonium methylide. Rearrangement of epoxide (XVII) in the presence of molecular sieves furnished aldehyde (XVII), which was converted to acid (IX) by oxidation with sodium chlorite.
| 【2】 Arai, H.; Tanaka, K.; Watanabe, I.; Kodama, T.; Hirano, H.; Abe, N.; Nakabayashi, M. (Toyama Chemical Co., Ltd.); Novel 2-[4-(3-methyl-2-thienyl)phenyl]propionic acid and pharmaceutically acceptable salt thereof and method for treating symptoms of inflammation and pain. US 4230719 . |
| 【1】 Kodama, T.; Nakabayashi, M.; Watanabe, I.; Hirano, Y.; Abe, N.; Tanaka, K.; Arai, H. (Toyama Chemical Co., Ltd.); 2-[4-(3-Methyl-2-thienyl)phenyl]propionic acid derivs. and its non-toxic salts. DE 2850485; JP 1981049376 . |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (IX) | 62687 | 2-[4-(3-methyl-2-thienyl)phenyl]propanoic acid | C14H14O2S | 详情 | 详情 | |
| (XIV) | 62689 | 1-[4-(3-methyl-2-thienyl)phenyl]-1-ethanone | C13H12OS | 详情 | 详情 | |
| (XVII) | 62692 | 2-[4-(3-methyl-2-thienyl)phenyl]propanal | C14H14OS | 详情 | 详情 | |
| (XXI) | 62695 | 2-methyl-2-[4-(3-methyl-2-thienyl)phenyl]oxirane | C14H14OS | 详情 | 详情 |
合成路线5
该中间体在本合成路线中的序号：(IX)In an alternative procedure, acetophenone (XIV) was condensed with KCN in the presence of ammonium carbonate to produce hydantoin (XXII). Basic hydrolysis of (XXII) led to amino acid (XXIII), which was converted to the dimethylamino analogue (XXIV) by reductive alkylation under Eschweiler-Clarke conditions. The desired arylpropionic acid (IX) was obtained from (XXIV) by hydrogenolysis in the presence of Pd/C
| 【2】 Arai, H.; Tanaka, K.; Watanabe, I.; Kodama, T.; Hirano, H.; Abe, N.; Nakabayashi, M. (Toyama Chemical Co., Ltd.); Novel 2-[4-(3-methyl-2-thienyl)phenyl]propionic acid and pharmaceutically acceptable salt thereof and method for treating symptoms of inflammation and pain. US 4230719 . |
| 【1】 Kodama, T.; Nakabayashi, M.; Watanabe, I.; Hirano, Y.; Abe, N.; Tanaka, K.; Arai, H. (Toyama Chemical Co., Ltd.); 2-[4-(3-Methyl-2-thienyl)phenyl]propionic acid derivs. and its non-toxic salts. DE 2850485; JP 1981049376 . |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (IX) | 62687 | 2-[4-(3-methyl-2-thienyl)phenyl]propanoic acid | C14H14O2S | 详情 | 详情 | |
| (XIV) | 62689 | 1-[4-(3-methyl-2-thienyl)phenyl]-1-ethanone | C13H12OS | 详情 | 详情 | |
| (XXII) | 62696 | 5-methyl-5-[4-(3-methyl-2-thienyl)phenyl]-2,4-imidazolidinedione | C15H14N2O2S | 详情 | 详情 | |
| (XXIII) | 62697 | 2-[4-(3-methyl-2-thienyl)phenyl]alanine | C14H15NO2S | 详情 | 详情 | |
| (XXIV) | 62698 | N,N-dimethyl-2-[4-(3-methyl-2-thienyl)phenyl]alanine | C16H19NO2S | 详情 | 详情 |
合成路线6
该中间体在本合成路线中的序号：(IX)The thienyl bromobenzene (XXVII) was converted to the corresponding Grignard reagent and subsequently treated with ZnCl2 to afford the organozinc derivative (XXVIII). Condensation of (XXVIII) with ethyl bromopropionate (XXIX) led to the arylpropionic ester (XXX), which was further hydrolyzed to acid (IX) under basic conditions.
| 【2】 Arai, H.; Tanaka, K.; Watanabe, I.; Kodama, T.; Hirano, H.; Abe, N.; Nakabayashi, M. (Toyama Chemical Co., Ltd.); Novel 2-[4-(3-methyl-2-thienyl)phenyl]propionic acid and pharmaceutically acceptable salt thereof and method for treating symptoms of inflammation and pain. US 4230719 . |
| 【1】 Kodama, T.; Nakabayashi, M.; Watanabe, I.; Hirano, Y.; Abe, N.; Tanaka, K.; Arai, H. (Toyama Chemical Co., Ltd.); 2-[4-(3-Methyl-2-thienyl)phenyl]propionic acid derivs. and its non-toxic salts. DE 2850485; JP 1981049376 . |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (IX) | 62687 | 2-[4-(3-methyl-2-thienyl)phenyl]propanoic acid | C14H14O2S | 详情 | 详情 | |
| (XXVII) | 62700 | 2-(4-bromophenyl)-3-methylthiophene | C11H9BrS | 详情 | 详情 | |
| (XXVIII) | 62701 | chloro[4-(3-methyl-2-thienyl)phenyl]zinc | C11H9ClSZn | 详情 | 详情 | |
| (XXIX) | 19460 | ethyl 2-bromopropanoate; 2-Bromopropionic acid ethyl ester | 535-11-5 | C5H9BrO2 | 详情 | 详情 |
| (XXX) | 62702 | ethyl 2-[4-(3-methyl-2-thienyl)phenyl]propanoate | C16H18O2S | 详情 | 详情 |
合成路线7
该中间体在本合成路线中的序号：(IX)Glycidonitrile (XXXII) was prepared by condensation of ketone (XIV) with chloroacetonitrile (XXXI) under Darzens conditions. Epoxide ring opening in (XXXII) by HCl in toluene provided the chlorohydrin (XXXIII). Acetylation of (XXXIII), followed by dehydrohalogenation led to the acetoxy acrylonitrile (XXXIV). Hydrolysis and decarbonylation of (XXXIV) provided an alternative access to the arylpropionic acid (IX)
| 【2】 Arai, H.; Tanaka, K.; Watanabe, I.; Kodama, T.; Hirano, H.; Abe, N.; Nakabayashi, M. (Toyama Chemical Co., Ltd.); Novel 2-[4-(3-methyl-2-thienyl)phenyl]propionic acid and pharmaceutically acceptable salt thereof and method for treating symptoms of inflammation and pain. US 4230719 . |
| 【1】 Kodama, T.; Nakabayashi, M.; Watanabe, I.; Hirano, Y.; Abe, N.; Tanaka, K.; Arai, H. (Toyama Chemical Co., Ltd.); 2-[4-(3-Methyl-2-thienyl)phenyl]propionic acid derivs. and its non-toxic salts. DE 2850485; JP 1981049376 . |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (IX) | 62687 | 2-[4-(3-methyl-2-thienyl)phenyl]propanoic acid | C14H14O2S | 详情 | 详情 | |
| (XIV) | 62689 | 1-[4-(3-methyl-2-thienyl)phenyl]-1-ethanone | C13H12OS | 详情 | 详情 | |
| (XXXI) | 14443 | 2-chloroacetonitrile; chloroacetonitrile | 107-14-2 | C2H2ClN | 详情 | 详情 |
| (XXXII) | 62703 | 3-methyl-3-[4-(3-methyl-2-thienyl)phenyl]-2-oxiranecarbonitrile | C15H13NOS | 详情 | 详情 | |
| (XXXIII) | 62704 | 3-chloro-2-hydroxy-3-[4-(3-methyl-2-thienyl)phenyl]butanenitrile | C15H14ClNOS | 详情 | 详情 | |
| (XXXIV) | 62705 | (Z)-1-cyano-2-[4-(3-methyl-2-thienyl)phenyl]-1-propenyl acetate | C17H15NO2S | 详情 | 详情 |
合成路线8
该中间体在本合成路线中的序号：(IX)The glycidic ester (XV), obtained as in Scheme 2, was alternatively rearranged to the alpha-keto ester enol form (XXXV) under acidic conditions. Hydrolysis and decarbonylation of (XXXV) employing NaOMe furnished acid (XI)
| 【2】 Arai, H.; Tanaka, K.; Watanabe, I.; Kodama, T.; Hirano, H.; Abe, N.; Nakabayashi, M. (Toyama Chemical Co., Ltd.); Novel 2-[4-(3-methyl-2-thienyl)phenyl]propionic acid and pharmaceutically acceptable salt thereof and method for treating symptoms of inflammation and pain. US 4230719 . |
| 【1】 Kodama, T.; Nakabayashi, M.; Watanabe, I.; Hirano, Y.; Abe, N.; Tanaka, K.; Arai, H. (Toyama Chemical Co., Ltd.); 2-[4-(3-Methyl-2-thienyl)phenyl]propionic acid derivs. and its non-toxic salts. DE 2850485; JP 1981049376 . |
合成路线9
该中间体在本合成路线中的序号：(IX)The chlorohydrin (XXXIII), obtained as in Scheme 8, was converted to enol ether (XXXVI) via O-alkylation with bromoethane and sodium amide, followed by basic dehydrohalogenation. Acid hydrolysis of enol ether (XXXVI) produced the keto nitrile (XXXVII), which was then hydrolyzed and decarbonylated to acid (IX)
| 【2】 Arai, H.; Tanaka, K.; Watanabe, I.; Kodama, T.; Hirano, H.; Abe, N.; Nakabayashi, M. (Toyama Chemical Co., Ltd.); Novel 2-[4-(3-methyl-2-thienyl)phenyl]propionic acid and pharmaceutically acceptable salt thereof and method for treating symptoms of inflammation and pain. US 4230719 . |
| 【1】 Kodama, T.; Nakabayashi, M.; Watanabe, I.; Hirano, Y.; Abe, N.; Tanaka, K.; Arai, H. (Toyama Chemical Co., Ltd.); 2-[4-(3-Methyl-2-thienyl)phenyl]propionic acid derivs. and its non-toxic salts. DE 2850485; JP 1981049376 . |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (IX) | 62687 | 2-[4-(3-methyl-2-thienyl)phenyl]propanoic acid | C14H14O2S | 详情 | 详情 | |
| (XXXIII) | 62704 | 3-chloro-2-hydroxy-3-[4-(3-methyl-2-thienyl)phenyl]butanenitrile | C15H14ClNOS | 详情 | 详情 | |
| (XXXVI) | 62707 | (Z)-2-ethoxy-3-[4-(3-methyl-2-thienyl)phenyl]-2-butenenitrile | C17H17NOS | 详情 | 详情 | |
| (XXXVII) | 62708 | 3-[4-(3-methyl-2-thienyl)phenyl]-2-oxobutanenitrile | C15H13NOS | 详情 | 详情 |
合成路线10
该中间体在本合成路线中的序号：(IX)A different strategy was based on the Knoevenagel condensation of ketone (XIV) with methyl cyanoacetate (XXXVIII) to produce the alkylidene cyanoacetate (XXXIX). Double-bond epoxidation by means of H2O2 led to (XL), which was further rearranged to keto amide (XLI). Decarboxylation of (XLI) under Hofmann rearrangement conditions furnished the arylpropionic acid (IX)
| 【2】 Arai, H.; Tanaka, K.; Watanabe, I.; Kodama, T.; Hirano, H.; Abe, N.; Nakabayashi, M. (Toyama Chemical Co., Ltd.); Novel 2-[4-(3-methyl-2-thienyl)phenyl]propionic acid and pharmaceutically acceptable salt thereof and method for treating symptoms of inflammation and pain. US 4230719 . |
| 【1】 Kodama, T.; Nakabayashi, M.; Watanabe, I.; Hirano, Y.; Abe, N.; Tanaka, K.; Arai, H. (Toyama Chemical Co., Ltd.); 2-[4-(3-Methyl-2-thienyl)phenyl]propionic acid derivs. and its non-toxic salts. DE 2850485; JP 1981049376 . |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (IX) | 62687 | 2-[4-(3-methyl-2-thienyl)phenyl]propanoic acid | C14H14O2S | 详情 | 详情 | |
| (XIV) | 62689 | 1-[4-(3-methyl-2-thienyl)phenyl]-1-ethanone | C13H12OS | 详情 | 详情 | |
| (XXXVIII) | 34458 | Cyanoacetic acid methyl ester; methyl 2-cyanoacetate | 105-34-0 | C4H5NO2 | 详情 | 详情 |
| (XXXIX) | 62709 | methyl (E)-2-cyano-3-[4-(3-methyl-2-thienyl)phenyl]-2-butenoate | C17H15NO2S | 详情 | 详情 | |
| (XL) | 62710 | methyl 2-(aminocarbonyl)-3-methyl-3-[4-(3-methyl-2-thienyl)phenyl]-2-oxiranecarboxylate | C17H17NO4S | 详情 | 详情 | |
| (XLI) | 62711 | 3-[4-(3-methyl-2-thienyl)phenyl]-2-oxobutanamide | C15H15NO2S | 详情 | 详情 |
合成路线11
该中间体在本合成路线中的序号：(IX)Methylation of arylacetic ester (XLII) was accomplished via Claisen condensation with diethyl carbonate and alkylation of the resultant arylmalonate (XLIII) with iodomethane and NaOMe. The methylated compound (XLIV) was further subjected to hydrolysis and decarboxylation to give (IX)
| 【2】 Arai, H.; Tanaka, K.; Watanabe, I.; Kodama, T.; Hirano, H.; Abe, N.; Nakabayashi, M. (Toyama Chemical Co., Ltd.); Novel 2-[4-(3-methyl-2-thienyl)phenyl]propionic acid and pharmaceutically acceptable salt thereof and method for treating symptoms of inflammation and pain. US 4230719 . |
| 【1】 Kodama, T.; Nakabayashi, M.; Watanabe, I.; Hirano, Y.; Abe, N.; Tanaka, K.; Arai, H. (Toyama Chemical Co., Ltd.); 2-[4-(3-Methyl-2-thienyl)phenyl]propionic acid derivs. and its non-toxic salts. DE 2850485; JP 1981049376 . |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (IX) | 62687 | 2-[4-(3-methyl-2-thienyl)phenyl]propanoic acid | C14H14O2S | 详情 | 详情 | |
| (XLII) | 62712 | ethyl 2-[4-(3-methyl-2-thienyl)phenyl]acetate | C15H16O2S | 详情 | 详情 | |
| (XLIII) | 62713 | diethyl 2-[4-(3-methyl-2-thienyl)phenyl]malonate | C18H20O4S | 详情 | 详情 | |
| (XLIV) | 62714 | diethyl 2-methyl-2-[4-(3-methyl-2-thienyl)phenyl]malonate | C19H22O4S | 详情 | 详情 |
合成路线12
该中间体在本合成路线中的序号：(IX)The iodophenyl propionic acid (XLVIII) was protected as the oxazoline (LII) via activation as the corresponding acid chloride (XLIX), which was condensed with 2-amino-2-methylpropanol (L) to yield amide (LI). Subsequent cyclization of hydroxy amide (LI) by treatment with phosphorus oxychloride led to oxazoline (LII). Palladium coupling between aryl iodide (LII) and the Grignard reagent (VIII) provided the biaryl adduct (LIII). The oxazoline (LIII) was then hydrolyzed to (IX) with sulfuric acid and AcOH
| 【2】 Arai, H.; Tanaka, K.; Watanabe, I.; Kodama, T.; Hirano, H.; Abe, N.; Nakabayashi, M. (Toyama Chemical Co., Ltd.); Novel 2-[4-(3-methyl-2-thienyl)phenyl]propionic acid and pharmaceutically acceptable salt thereof and method for treating symptoms of inflammation and pain. US 4230719 . |
| 【1】 Kodama, T.; Nakabayashi, M.; Watanabe, I.; Hirano, Y.; Abe, N.; Tanaka, K.; Arai, H. (Toyama Chemical Co., Ltd.); 2-[4-(3-Methyl-2-thienyl)phenyl]propionic acid derivs. and its non-toxic salts. DE 2850485; JP 1981049376 . |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (VIII) | 36973 | bromo(3-methyl-2-thienyl)magnesium | C5H5BrMgS | 详情 | 详情 | |
| (IX) | 62687 | 2-[4-(3-methyl-2-thienyl)phenyl]propanoic acid | C14H14O2S | 详情 | 详情 | |
| (XLVIII) | 62718 | 2-(4-iodophenyl)propanoic acid | C9H9IO2 | 详情 | 详情 | |
| (XLIX) | 62719 | 2-(4-iodophenyl)propanoyl chloride | C9H8ClIO | 详情 | 详情 | |
| (L) | 21513 | 2-amino-2-methyl-1-propanol；Karl Fischer;2-Amino-2-methyl-propan-1-ol；2-amino-2-methyl-1-propanol | 124-68-5 | C4H11NO | 详情 | 详情 |
| (LI) | 62720 | N-(2-hydroxy-1,1-dimethylethyl)-2-(4-iodophenyl)propanamide | C13H18INO2 | 详情 | 详情 | |
| (LII) | 62721 | 2-[1-(4-iodophenyl)ethyl]-4,4-dimethyl-4,5-dihydro-1,3-oxazole | C13H16INO | 详情 | 详情 | |
| (LIII) | 62722 | 4,4-dimethyl-2-{1-[4-(3-methyl-2-thienyl)phenyl]ethyl}-4,5-dihydro-1,3-oxazole | C18H21NOS | 详情 | 详情 |