| 83% |
With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; sodium carbonate; In 1,2-dimethoxyethane; water; at 80℃; for 18h;Inert atmosphere; |
100 mg of palladium on carbon (10 wt % of palladium) was added into 5 mL of methanol (MeOH) so as to prepare a suspension of palladium on carbon. 1.0 g of 4-allylanisole (compound 9) (Aldrich) was dissolved in 10 mL of MeOH so as to form a solution of 4-allylanisole. The solution of 4-allylanisole was mixed with the suspension of palladium on carbon, followed by stirring under a hydrogen pressure of 60 psi for 2 hours (TLC monitoring). The resultant mixture was subjected to a filtration treatment so as to remove all of the solids therein. Subsequently, an evaporation process was conducted such that a crude residue was obtained. 1.0 g of the crude residue was dissolved in 10 mL of acetic acid (AcOH). To the resultant solution was slowly added 0.5 mL of bromine. The resultant mixture was stirred at ambient temperature for 18 hours (TLC monitoring). An evaporation process under vacuum was performed, followed by an extraction treatment with 20 mL of EtOAc. The extract was washed thoroughly with a saturated Na2S2O3 solution (10 mL), a NaHCO3 solution (10 mL), and brine (3*10 mL). The organic layer was subjected to a concentration process under reduced pressure such that a concentrated product was obtained (1.2 g, 78% yield). 500 mg of the concentrated product and 800 mg of <strong>[889865-38-7]4-(tetrahydro-2H-pyran-2-yloxy)-phenylboronic acid pinacol ester</strong> (compound 4) were added in 8 mL of DME. To the resultant solution was added 89 mg of the catalyst, PdCl2(dppf).CH2Cl2, under argon, followed by adding 3 mL of an aqueous Na2CO3 solution (2 M). The resultant mixture was stirred at 80 C. for 18 hours. An evaporation process was conducted. A dark residue was formed and was then subjected to an extraction treatment using EtOAc. The organic layer was repeatedly washed with brine (3*20 mL), and was subjected to a concentration process under reduced pressure. The resultant dark brown oil was subjected to a purification treatment employing silica gel column chromatography (EtOAc-hexane (1:19) as a mobile phase). Therefore, 2-(2'-methoxy-5'-propyl-biphenyl-4-yloxy)-tetrahydro-pyran (compound 10) as a gum was obtained (83% yield). |
| 593 mg |
With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; sodium carbonate; In 1,2-dimethoxyethane; water; at 80℃; for 18h;Inert atmosphere; |
To a suspension solution of palladium on carbon (100 mg, 10% by weight) in MeOH (5 mL) was added a solution of 9 (1.0 g, 6.75 mmol) in MeOH (10 mL) and the resulting mixture was stirred under 60 psi hydrogen pressure in the Parr Hydrogenator for 2 h at which time TLC indicated complete disappearance of the starting material. The mixture was filtered to get rid of all the solid materials and after evaporation of the solvent afforded a crude residue. To the solution of the residue (1.0 g, 6.75 mmol) in AcOH (10 mL) was slowly added excess bromine (0.5 mL). The mixture was stirred for 18 h at ambient temperature when TLC indicated total disappearance of the starting material. Solvent was evaporated under vacuum and the residue was extracted with ethyl acetate (20 mL), and the extract was washed thoroughly with saturated Na2S2O3 solution (10 mL), NaHCO3 solution (10 mL) and brine (3 × 10 mL). The organic layer was concentrated under reduced pressure and the crude residue (1.2 g, 5.26 mmol, 78%) was used directly in the next step without further purification. To the solution of crude residue (500 mg, 2.19 mmol) from the previous step and 4 (800 mg, 2.63 mmol) in DME (8 mL) was added the catalyst PdCl2(dppf)·CH2Cl2 (89 mg, 0.109 mmol) under argon atmosphere followed by Na2CO3 solution (3 mL, aq. 2 M) and the mixture was stirred at 80 C for 18 h. Evaporation of solvent afforded a dark residue which was extracted with EtOAc and the organic extract was repeatedly washed with brine (3 × 20 mL). The organic layer was concentrated under reduced pressure to furnish a dark brown oil which was purified by column chromatography using a mixture of EtOAc and hexanes (1:19) as mobile phase to yield pure 10 (gum, 593 mg, 1.81 mmol, 83%). 1H NMR (400 MHz, CDCl3, delta): 7.51 (d, J = 2.1 Hz, 2H), 7.30 (m, 4H merged with doublet), 6.91 (d, J = 8.3 Hz, 1H), 5.49 (t, J = 3.2 Hz, 1H), 3.94 (m, 1H), 3.81 (s, 3H), 3.62 (m, 1H), 2.60 (t, J = 7.4 Hz, 2H), 2.05 (m, 1H), 1.91 (m, 2H), 1.72-1.65 ( m, 5H, merged with a quatrate), 0.99 (t, J = 7.4 Hz, 3H). 13C NMR (100.6 MHz, CDCl3, delta): 156.2, 154.6, 134.9, 132.0, 130.9, 130.5, 130.0, 127.9, 111.2, 96.4, 62.0, 55.7, 37.3, 30.5, 25.3, 24.9, 18.8, 13.9. IR (neat): 2952, 2871, 1608, 1513, 1492, 1463, 1454, 1440, 1402, 1384, 1355, 1263 cm-1. EIMS (70 eV) m/z: 326.3 (1.1), 242.2 (100), 213.2 (54.4), 197.1 (5.2), 170.1 (3.2), 141.1 (2.6), 115.1 (3.5), 85.1 (8.8). HRMS-EI (m/z): M+ calcd for C21H26O3, 326.1882; found 326.1885. |
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