(5-氯-2,3-二氢苯并呋喃-2-基)甲醇

反应条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To a solution of (5-chloro-2,3-dihydro-1-benzofuran-2-yl)methanol (2 g, 11 mmol), KHCO3 (4.32 g, 43 mmol, 4 eq) and TEMPO (20 mg, 0.13 mmol, 0.1 eq) in water (8 ml) and CH3CN (18 ml) was added NaOCl (20 ml, aq. 15%, ˜4 eq) dropwise with stirring at 0° C. and stirred for 1 hour. The mixture was diluted with water (200 ml) and adjusted to pH˜4 with hydrogen chloride (2N). After extraction with ethyl acetate (3×200 ml), the organic layers were combined, washed with brine (200 ml), dried over anhydrous sodium sulfate, filtered, and then concentrated under vacuum. The crude material was purified by silica gel chromatography using 1% methanol in dichloromethane to elute. The product-containing fractions were combined and concentrated under vacuum to afford 5-chloro-2,3-dihydro-1-benzofuran-2-carboxylic acid as a yellow solid (1.6 g, 74%). 1H NMR (300 MHz, CDCl3): δ 7.05-7.22 (m, 2H), 6.83 (d, J=8.4 Hz, 1H), 5.20-5.30 (m, 1H), 3.56-3.65 (m, 1H), 3.33-3.45 (m, 1H) stirred for 1 hour After extraction with ethyl acetate (3×200 ml) washed with brine (200 ml) dried over anhydrous sodium sulfate filtered concentrated under vacuum The crude material was purified by silica gel chromatography to elute concentrated under vacuum

反应条件: temp:50.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To a solution of 4-chloro-2-(prop-2-en-1-yl)phenol (17 g, crude, nominally 101 mmol) in chloroform (100 ml) was added mCPBA (17.4 g, 101 mmol, 1 eq) with stirring for 1 h at 50° C. in an oil bath. Then the reaction mixture was concentrated under vacuum and re-dissolved in MeOH (100 ml). Potassium carbonate (27.6 g, 200 mmol, 2 eq) was added and the mixture was stirred for 5 hours at 50° C. The solids were filtered off and the filtrate was concentrated under vacuum. The crude material was purified by silica gel chromatography using 3% ethyl acetate in petroleum ether to elute. The product-containing fractions were combined and concentrated under vacuum to afford (5-chloro-2,3-dihydro-1-benzofuran-2-yl)methanol as yellow oil (6.15 g); 1H NMR (300 MHz, CDCl3): δ 7.00-7.18 (m, 2H), 6.80 (d, J=8.7 Hz, 1H), 4.88-4.97 (m, 1H), 3.85-3.90 (m, 1H), 3.70-3.79 (m, 1H), 3.19-3.27 (dd, J=9.3 Hz, 15.9 Hz, 1H), 2.98-3.05 (dd, J=7.5 Hz, 15.9 Hz, 1H), 2.10 (broad s, 1H). Then the reaction mixture was concentrated under vacuum re-dissolved in MeOH (100 ml) the mixture was stirred for 5 hours at 50° C The solids were filtered off the filtrate was concentrated under vacuum The crude material was purified by silica gel chromatography to elute concentrated under vacuum

反应条件: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To a solution of (5-chloro-2,3-dihydro-1-benzofuran-2-yl)methanol (3 g, 16 mmol) in benzene (50 ml) was added pyridine (1.55 g, 19.6 mmol, 1.2 eq) and thionyl chloride (2.72 g, 23.0 mmol) dropwise with stirring at 0° C. for 7 hours at 80° C. in an oil bath. The reaction mixture was adjusted to ˜pH 8 with aqueous sodium bicarbonate and then extracted with ethyl acetate (3×50 mL). The organic layers were combined, dried over anhydrous magnesium sulfate, filtered, and concentrated under vacuum. The crude material was purified by silica gel chromatography using 3% ethyl acetate in petroleum ether to elute. The product-containing fractions were combined and concentrated under vacuum to afford 5-chloro-2-(chloromethyl)-2,3-dihydro-1-benzofuran as an off-white solid (1.5 g, 46%); 1H NMR (300 MHz, CDCl3): δ 7.06-7.14 (m, 2H), 6.70 (d, J=8.4 Hz, 1H), 4.99-5.10 (m, 1H), 3.64-3.76 (m, 2H), 3.32-3.40 (dd, J=9.3 Hz, 16.2 Hz, 1H), 3.09-3.17 (dd, J=6.6 Hz, 16.2 Hz. 1H). extracted with ethyl acetate (3×50 mL) dried over anhydrous magnesium sulfate filtered concentrated under vacuum The crude material was purified by silica gel chromatography to elute concentrated under vacuum

反应条件: temp:50.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To a solution of 4-chloro-2-(prop-2-en-1-yl)phenol (17 g, crude, nominally 101 mmol) in chloroform (100 ml) was added mCPBA (17.4 g, 101 mmol, 1 eq) with stirring for 1 hour at 50° C. in an oil bath. Then the reaction mixture was concentrated under vacuum and re-dissolved in MeOH (100 ml). Potassium carbonate (27.6 g, 200 mmol, 2 eq) was added and the mixture was stirred for 5 hours at 50° C. The solids were filtered off and the filtrate was concentrated under vacuum. The crude material was purified by silica gel chromatography using 3% ethyl acetate in petroleum ether to elute. The product-containing fractions were combined and concentrated under vacuum to afford (5-chloro-2,3-dihydro-1-benzofuran-2-yl)methanol as yellow oil (6.15 g); 1H NMR (300 MHz, CDCl3): δ 7.00-7.18 (m, 2H), 6.80 (d, J=8.7 Hz, 1H), 4.88-4.97 (m, 1H), 3.85-3.90 (m, 1H), 3.70-3.79 (m, 1H), 3.19-3.27 (dd, J=9.3 Hz, 15.9 Hz, 1H), 2.98-3.05 (dd, J=7.5 Hz, 15.9 Hz, 1H), 2.10 (broad s, 1H). Then the reaction mixture was concentrated under vacuum re-dissolved in MeOH (100 ml) the mixture was stirred for 5 hours at 50° C The solids were filtered off the filtrate was concentrated under vacuum The crude material was purified by silica gel chromatography to elute concentrated under vacuum