Reference of 13674-16-3 , The common heterocyclic compound, 13674-16-3, name is Methyl 2-hydroxy-3-phenylpropanoate, molecular formula is C10H12O3, its traditional synthetic route has been very mature, but the traditional synthetic route has various shortcomings, such as complicated route, low yield, poor purity, etc., below Introduce a new synthetic route.
Phenyltrimethylammoniun tribromide (9.45 g, 25.1 mmol) was added under nitrogen in portions over approximately 2 h to a solution of 1-(6-methoxy-naphthalen-2-yl)-ethanone (5.05 g, 25.2 mmol) in 50 mL of anhydrous THF at room temperature. After the addition the reaction was stirred at room temperature for 0.5 h. and then 250 mL of cold water was added. The solid present was collected by filtration, rinsed with 50 mL of water and dried under reduced pressure to give 6.66 g of a tan solid. Recrystallization of the solid from isopropyl alcohol gave 2-bromo-1-(6-methoxy-2-naphthyl)ethanone (4.07 g, 58%) as a brown solid, mp 109-112 C. Elemental Analysis for C13H11BrO2Calc’d: C, 55.94; H, 3.97; N, 0.00. Found: C, 56.03; H, 3.94; N, 0.00. Step 2: 4-(6-methoxy-2-naphthyl)-2-phenyl-1,3-thiazole. Thiobenzamide (447 mg, 3.26 mmol) was added under nitrogen to a solution of (2-bromo-1-(6-methoxy-2-naphthyl)ethanone (906 mg, 3.25 mmol), prepared in the previous step, in 25 mL of absolute ethanol at approximately 70 C. After the addition the reaction was refluxed for 2 h. The solid was collected by filtration, rinsed with absolute ethanol and dried under reduced pressure to give 4-(6-methoxy-2-naphthyl)-2-phenyl-1,3-thiazole (909 mg, 88%) as a white solid, mp 191-193 C. Elemental Analysis for C20H15NOS Calc’d: C, 75.68; H, 4.76; N, 4.41. Found: C, 75.37; H, 4.65; N, 4.31. Step 3: 6-(2-phenyl-1,3-thiazol-4-yl)-2-naphthol. A solution of 4-(6-methoxy-2-naphthyl)-2-phenyl-1,3-thiazole (804 mg, 2.53 mmol), prepared in the previous step, in 50 mL of glacial HOAc plus 25 mL of 48% HBr was stirred under nitrogen at 120 C. for 3 h. The solvent was removed under reduced pressure and the residue partitioned between 10% methanol-methylene chloride and 5% NaHCO3. (Note: The solid that did not dissolve in either layer was collected by filtration and saved as the HCL salt of the desired product). The aqueous layer was separated and extracted three times with 10% methanol-methylene chloride. The combined extracts were dried (MgSO4), filtered and the solvent removed under reduced pressure to give 6-(2-phenyl-1,3-thiazol-4-yl)-2-naphthol (650 mg, 85%) as a brown solid, mp 194-197 C. Elemental Analysis for C19H13NOS Calc’d: C, 75.22; H, 4.32; N, 4.62. Found: C, 74.22; H, 4.12; N, 4.43 Step 4: 2-Hydroxy-3-phenyl-propionic acid methyl ester. Hydrogen chloride was bubbled for 15 minutes into a solution of 2-hydroxy-3-phenyl-propionic acid (10.0 g, 60 mmol) in 100 mL of methanol at room temperature. The vessel was sealed and then stirred overnight at room temperature. The reaction was made basic by the addition of 5% NaHCO3 and then concentrated under reduced pressure to remove the methanol. The residue was diluted with water and extracted with ethyl acetate. The organic layer was extracted with saturated NaCl, dried (MgSO4), filtered and the solvent removed under reduced pressure to give 2-hydroxy-3-phenyl-propionic acid methyl ester (9.7 g, 90%) as a yellow oil, MS m/z 180 [M]+. Elemental Analysis for C10H12O3 Calc’d: C, 66.65; H, 6.71; N, 0.00. Found: C, 66.52; H, 6.86; N, 0.29 Step 5: 3-Phenyl-2-trifluoromethanesulfonyloxy-propionic acid methyl ester. Triethylamine (931 muL, 6.68 mmol) was added under nitrogen to a solution of 2-hydroxy-3-phenyl-propionic acid methyl ester (1.00 g, 5.57 mmol), prepared in the previous step, in 20 mL of chloroform (99.9%; free of ethanol) at dry ice-acetone temperature. Trifluoromethanesulfonic anhydride (1.03 mL, 6.13 mmol) was then added dropwise over 15 minutes. The cooling bath was removed and the reaction was stirred overnight at room temperature. The reaction was extracted with 1 N HCl, 5% NaHCO3, dried (MgSO4), filtered and the solvent removed under reduced pressure to give 1.53 g a brown oil. Purification of the oil on 100 g of silica gel (230-400 mesh) using 3:1 methylene chloride:hexane as the eluent gave 3-phenyl-2-trifluoromethanesulfonyloxy-propionic acid methyl ester (1.106 g, 64%) as clear oil. Elemental Analysis for C11H11F3O5S Calc’d: C, 42.31; H, 3.55; N, 0.00. Found: C, 42.15; H, 3.35; N, 0.14 Step 6: Methyl 3-phenyl-2-{[6-(2-phenyl-1,3-thiazol-4-yl)-2-naphthyl]oxy} propanoate. A mixture of 6-(2-phenyl-1,3-thiazol-4-yl)-2-naphthol (247 mg, 0.814 mmol), prepared in step 3,3-phenyl-2-trifluoromethanesulfonyloxy-propionic acid methyl ester (387 mg, 1.24 mmol), prepared in the previous step, and cesium carbonate (532 mg, 1.63 mmol) in 20 mL of acetone was stirred under nitrogen at room temperature for 17 h. The reaction was concentrated under reduced pressure to remove the acetone. The residue was partitioned between methylene chloride and water. The aqueous layer was separated and extracted three times with methylene chloride. The combined extracts were dried (MgSO4), filtered and the solvent removed under reduced pressure to give 449 mg of a brown oil. Purification of the oil on 300 g of silica gel (230-400 mesh) using 1:1 to 3:2 methylene chloride:hexane as the eluent gave methyl 3-phenyl-2…
The synthetic route of 13674-16-3 has been constantly updated, and we look forward to future research findings.
Reference:
Patent; WYETH; US2006/52420; (2006); A1;,
Alcohol – Wikipedia,
Alcohols – Chemistry LibreTexts