【结 构 式】 |
【分子编号】68879 【品名】Toluene-4-sulfonic acid 3-methylsulfanyl-propyl ester;3-(METHYLTHIO)-1-(TOSYLOXY)PROPANE;3-(methylthio)propyl 4-methylbenzenesulfonate 【CA登记号】187722-18-5 |
【 分 子 式 】C11H16O3S2 【 分 子 量 】260.378 【元素组成】C 50.74% H 6.19% O 18.43% S 24.63% |
合成路线1
该中间体在本合成路线中的序号:(X)Suzuki coupling of 4-bromo-3,5-dimethylphenol (I) with 3-formylphenylboronic acid (II) in the presence of Pd(PPh)3 and Na2CO3 in EtOH/toluene at 80 °C affords 4’-hydroxy-2’,6’-dimethylbiphenyl-3-carbaldehyde (III), which is then condensed with 3-(methylsulfonyl)propyl tosylate (IV) by means of K2CO3 at 90 °C in DMF to give 2’,6’-dimethyl-4’-[3-(methylsulfonyl)propoxy]biphenyl-3-carbaldehyde (V). Reduction of aldehyde (V) with NaBH4 in MeOH/THF at 0 °C produces the corresponding alcohol (VI), which upon Mitsunobu condensation with methyl [6-hydroxy-2,3-dihydro-1-benzofuran-3(S)-yl]acetate (VII) in the presence of Bu3P and ADDP in toluene yields the corresponding ether (VIII). Finally, ester (VIII) is hydrolyzed with NaOH in MeOH/THF/H2O at 50 °C .
3-(Methylsulfonyl)propyl tosylate (IV) is prepared by sulfonylation of 3-(methylsulfanyl)-1-propanol (IX) using TsCl in the presence of TMHDA and Et3N in toluene to produce the corresponding tosylate (X), which is finally oxidized with oxone in MeOH/H2O .
【1】 Negoro, N., Sasaki, S., Mikami, S. et al. Discovery of TAK-875: A potent, selective, and orally bioavailable GPR40 agonist. ACS Med Chem Lett 2010, 1: 290-4. |
【2】 Yasuma, T., Negoro, N., Yamashita, M., Itou, M. (Takeda Pharmaeutical Co., Ltd.). Fused cyclic compounds. CA 2656003, EP 2041123, EP 2248812, JP 2009280585, JP 2009542580, US 2010004312, US 7732626, WO 2008001931. |
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) | 68874 | 4-bromo-3,5-dimethylphenol;4-Bromo-3,5-xylenol | 7463-51-6 | C8H9BrO | 详情 | 详情 |
(II) | 57061 | 3-(Dihydroxyboryl)benzaldehyde; 3-Boronobenzaldehyde; 3-Formylbenzeneboronic acid; 3-Formylphenylboronic acid; Benzaldehyde-3-boronic acid | 87199-16-4 | C7H7BO3 | 详情 | 详情 |
(III) | 68875 | 4'-hydroxy-2',6'-dimethyl-[1,1'-biphenyl]-3-carbaldehyde | C15H14O2 | 详情 | 详情 | |
(IV) | 68877 | 3-(methylsulfonyl)propyl tosylate;3-(methylsulfonyl)propyl 4-methylbenzenesulfonate | C11H16O5S2 | 详情 | 详情 | |
(V) | 68876 | 2’,6’-dimethyl-4’-[3-(methylsulfonyl)propoxy]biphenyl-3-carbaldehyde;2',6'-dimethyl-4'-(3-(methylsulfonyl)propoxy)-[1,1'-biphenyl]-3-carbaldehyde | C19H22O4S | 详情 | 详情 | |
(VI) | 68878 | (2',6'-dimethyl-4'-(3-(methylsulfonyl)propoxy)-[1,1'-biphenyl]-3-yl)methanol | C19H24O4S | 详情 | 详情 | |
(VII) | 68881 | methyl [6-hydroxy-2,3-dihydro-1-benzofuran-3(S)-yl]acetate;(S)-methyl 2-(6-hydroxy-2,3-dihydrobenzofuran-3-yl)acetate | C11H12O4 | 详情 | 详情 | |
(VIII) | 68881 | methyl [6-hydroxy-2,3-dihydro-1-benzofuran-3(S)-yl]acetate;(S)-methyl 2-(6-hydroxy-2,3-dihydrobenzofuran-3-yl)acetate | C11H12O4 | 详情 | 详情 | |
(IX) | 68880 | 3-Methylthiopropanol;3-(Methylthio)propanol;3-Methylthio-1-propanol;3-(methylthio)propan-1-ol;3-(methylsulfanyl)-1-propanol | 505-10-2 | C4H10OS | 详情 | 详情 |
(X) | 68879 | Toluene-4-sulfonic acid 3-methylsulfanyl-propyl ester;3-(METHYLTHIO)-1-(TOSYLOXY)PROPANE;3-(methylthio)propyl 4-methylbenzenesulfonate | 187722-18-5 | C11H16O3S2 | 详情 | 详情 |