m-Chloroperbenzoic acid → 5-Benzyloxy-2-methylpyridine 1-oxide

The title compound was synthesized by referring to Tetrahedron, 2001, 57, 3479. To a solution of 3-hydroxy-6-methylpyridine (5.0 g) in methanol (100 ml) was added an aqueous solution of SN sodium hydroxide (9.2 ml), and the solution was stirred for 15 minutes at room temperature. The solvent was evaporated in vacuo, toluene was added thereto, and to the residue obtained by evaporating the solvent in vacuo, were sequentially added N,N-dimethylformamide (100 ml) and benzyl bromide (5.5 ml) under a nitrogen atmosphere, and the solution was stirred for 30 minutes at 60° C. Water was added thereto followed by stirring, the solution was extracted with ethyl acetate, then sequentially washed with water and brine, dried over anhydrous magnesium sulfate, and then the solvent was evaporated in vacuo. The residue was purified by silica gel column chromatography (hexane-ethyl acetate system) to obtain 5-benzyloxy-2-methylpyridine (7.4 g). To a solution of 65% 3-chloroperbenzoic acid (13 g) in dichloromethane (200 ml) was added dropwise a solution of 5-benzyloxy-2-methylpyridine (9.7 g) in dichloromethane (16 ml) on an ice bath, and the solution was stirred for 5.5 hours at room temperature, which was then neutralized with a saturated aqueous solution of sodium bicarbonate. The solution was extracted with dichloromethane, then sequentially washed with water and brine, dried over anhydrous magnesium sulfate, then the solvent was evaporated in vacuo to obtain 5-benzyloxy-2-methylpyridine 1-oxide. This compound (10.4 g) was dissolved in acetic anhydride (120 ml), and the solution was stirred for 1.5 hours at 120° C. To the residue obtained by evaporating the solvent in vacuo were sequentially added an aqueous solution of 5N sodium hydroxide (50 ml) and ethanol (150 ml), and the solution was stirred for 30 minutes at 90° C. The insoluble material was filtered through celite pad, extracted with ethyl acetate, then sequentially washed with water and brine, dried over anhydrous magnesium sulfate, and then the solvent was evaporated in vacuo. The residue was purified by silica gel column chromatography (hexane-ethyl acetate system) to obtain (5-benzyloxypyridin-2-yl)methanol (7.2 g). To a solution of this compound (5.0 g) in chloroform (100 ml) were sequentially added triethylamine (13 ml) and dimethylsulfoxide (26 ml), the solution was stirred, sulfur trioxide pyridine complex (11 g) was added thereto on an ice bath, and the solution was stirred for 10 hours while warming to room temperature. Water and a saturated aqueous solution of sodium bicarbonate were sequentially added thereto followed by stirring, the solution was extracted with ethyl acetate, then sequentially washed with water and brine, dried over anhydrous magnesium sulfate, and then the solvent was evaporated in vacuo. The residue was purified by silica gel column chromatography (hexane-ethyl acetate system) to provide the title compound (3.8 g).

1. extractionThe solution was extracted with dichloromethane
2. washsequentially washed with water and brine
3. dry with materialdried over anhydrous magnesium sulfate
4. customthe solvent was evaporated in vacuo

ORD record

ord-e57b3fb27b92474eb2278715433cb2d4

Source dataset

uspto-grants-2011_06

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07960412B2