Synthesis from cyanuric chloride: To a solution of cyanuric chloride (368.8mg, 2.00 mmol) and benzyl alcohol (0.31 mL, 3.0 mmol) in CH2Cl2 (4.00mL) was added ethyldiisopropylamine (359 μL, 2.06 mmol) at 0 °C. After stirred for 1 h, the mixture was allowed to warm to RT. After stirred for additional 1 h, the mixture was cooled to 0 °C. Sodium acetate (492.2 mg, 6.00 mmol), isopropyl alcohol (4.00 mL), and N-methylmorpholine (110 μL, 1.00 mmol) was added at 0 °C. The mixture was stirred for 1 h at 0 °C and for 1 h at RT. After aqueous HCl (6 M, 0.33 mL) was added at 0 °C, the mixture was concentrated under reduced pressure. The residue was washed with cold water. Cesium carbonate (1.95 g, 6.00 mmol), DMSO (4.00 mL), and methyl iodide (374 L, 6.00 mmol) was added at RT. After stirred for 40 min, the mixture was diluted with EtOAc (20 mL) and washed with water (40 mL) and brine (20 mL). The organic layer was dried over Na2SO4, filtered, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (hexane/acetone = 2:1) to afford DMBOT (358.0 mg, 72%) as a crystalline solid.
Synthesis from MonoBOT: To a suspension of MonoBOT (109.6 mg, 0.500 mmol) and cesium carbonate (358 mg, 1.10 mmol) in DMSO (1.00 mL) was added methyl iodide (68.5 L, 1.10 mmol) at RT. After stirred for 40 min, the reaction mixture was diluted with EtOAc (10 mL) and washed with water (30 mL × 2) and brine (30 mL). The organic layer was dried over Na2SO4, filtered, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (hexane/EtOAc = 1:1) to afford DMBOT (111.2 mg, 90%) as a crystalline solid
Benzyl 3-phenylpropyl ether (2a): To a mixture of 1a (54.5 L, 0.400 mmol), DMBOT (118.7 mg, 0.480 mmol), and MS5A (6.7 mg) in 1,4-dioxane (1.33 mL) was added TfOH (3.5 L, 0.040 mmol) at RT. After stirred for 4 h, the reaction mixture was quenched with pyridine (32.0 μL), diluted with EtOAc (20 mL), and filtered to remove MS5A. The filtrate was washed with 1% (w/w) aqueous K2CO3 (10 mL) and brine (10 mL), dried over Na2SO4, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (hexane/EtOAc = 9:1) followed by recycling preparative HPLC to afford 2a (81.0 mg, 90%) as a clear colorless oil.
Benzyl 2-(trimethylsilyl)ethyl ether (2l): To a mixture of 1l (36.7 μL, 0.300 mmol), DMBOT (148.4 mg, 0.600 mmol), and MS5A (5.0 mg) in 1,4-dioxane (1.00 mL, 0.3 M) was added 6 (10.2 mg, 0.030 mmol) at RT. After stirred for 12 h, the reaction mixture was quenched with NEt3 (6.3 μL), diluted with EtOAc (5 mL) and filtered to remove MS5A. The filtrate was washed with 1% (w/w) aqueous K2CO3 (5 mL) and brine (5 mL), dried over Na2SO4, and concentrated under reduced pressure. The residue was purified by preparative TLC (hexane/acetone = 40:1) to afford 2l (45.8 mg,73%) as a clear colorless oil.
Eur. J. Org. Chem. 10.1002/ejoc.201601387