(2-Methylbenzo[d]oxazol-5-yl)Methanol

136663-21-3

136663-38-2

General procedure for the synthesis of (2-methylbenzo[d]oxazol-5-yl)methanol from methyl 2-methylbenzo[d]oxazole-5-carboxylate: 1. To a 250 mL round-bottomed flask under nitrogen protection were added methyl 3-amino-4-hydroxybenzoate (7.00 g, 41.88 mmol, 1.00 equiv), 1,1,1-trimethoxyethane (50 mL) and trifluoroacetic acid (5.2 mL). The reaction mixture was stirred at 25°C for 1.5 hours. 2. After completion of the reaction, the reaction solution was diluted with 100 mL of dichloromethane, and the organic phase was washed sequentially with 2 x 50 mL of saturated aqueous sodium bicarbonate and 1 x 100 mL of brine, dried over anhydrous sodium sulfate, and then concentrated under reduced pressure to give 7.60 g (crude) of methyl 2-methyl-1,3-benzoxazole-5-carboxylate as a light brown solid. 3. To a 100 mL three-necked round-bottomed flask under nitrogen protection was added methyl 2-methyl-1,3-benzoxazole-5-carboxylate (6.00 g, 31.38 mmol, 1.00 eq.) and oxolane (50 mL), and cooled to -20 °C. The mixture was then purified to -20 °C. 4. At -20 °C, lithium aluminum hydride (1.19 g, 35.08 mmol, 1.00 eq.) was added in batches and stirred for 1 hour. 5. Upon completion of the reaction, the reaction was quenched by the addition of 1.2 mL of water at -20 °C, followed by the addition of 3.6 mL of 15% aqueous sodium hydroxide and 1.2 mL of water for dilution. 6. Extract with 100 mL of ethyl acetate at room temperature, filter out the solids and concentrate the organic phase under reduced pressure. 7. The residue was purified by silica gel column chromatography with ethyl acetate/petroleum ether (1:10 to 1:1) as eluent to give 3.65 g (71% yield) of (2-methyl-1,3-benzoxazol-5-yl)methanol as a brown solid. Mass spectrum (ESI) m/z: 164 [M + H]+.