N-(furan-2-ylmethyl)methanesulfonamide

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Sodium hydride (60% mineral oil dispersion, 0.284 g, 7.1 mmol) was added in portions to a stirring solution of N-(furan-2-ylmethyl)methanesulfonamide (1.0 g, 5.7 mmol) in anhydrous N,N-dimethylformamide (12 mL), which was kept at 0° C. by an external ice bath. The ice bath was removed and the mixture was stirred for 50 mins at ambient temperature. 3-bromo-2-methylpropane (1.15 g, 8.6 mmol) was added in one portion, and the resulting mixture was stirred overnight at 65° C. before being diluted with ethyl acetate. The organic layer was successively washed with water and saturated aqueous sodium chloride solutions, dried (anhydrous sodium sulfate), filtered, and concentrated. The crude material was purified by silica gel column chromatography (0-50% ethyl acetate in hexanes) to give a clear liquid (1.24 g, 95%). 1H NMR (CDCl3, 300 MHz) δ 7.41-7.40 (m, 1H), 6.38-6.34 (m, 1H), 6.29-6.28 (m, 1H), 5.03-5.00 (m, 2H), 4.37 (s, 2H), 3.73 (s, 2H), 2.76 (s, 3H), 1.77 (s, 3H). was kept at 0° C. by an external ice bath The ice bath was removed the resulting mixture was stirred overnight at 65° C. The organic layer was successively washed with water and saturated aqueous sodium chloride solutions dried (anhydrous sodium sulfate) filtered concentrated The crude material was purified by silica gel column chromatography (0-50% ethyl acetate in hexanes)

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Sodium hydride (60% mineral oil dispersion, 0.524 g, 13.1 mmol) was added in portions to a 0° C. solution of N-(furan-2-ylmethyl)methanesulfonamide (2.0 g, 11.4 mmol) in 38 ml anhydrous N,N-dimethylformamide (38 mL), and the resultant mixture was allowed to warm to room temperature and stirred for 1 hour. Epibromohydrin (1.2 mL, 14.3 mmol) was added slowly, and the reaction was stirred for 3 hours at room temperature and 16 hours at 70° C. The reaction was cooled, diluted with ethyl acetate, and successively washed twice with water and once with saturated aqueous sodium chloride solutions. The organic layer was dried (anhydrous sodium sulfate), filtered, and concentrated under reduced pressure. The crude residue was purified by silica gel column chromatography (25-60% ethyl acetate in hexanes) to give a pale yellow liquid (2.2 g, 84%). 1H NMR (CDCl3, 300 MHz) δ 7.40-7.39 (m, 1H), 6.37-6.35 (m, 2H), 4.64-4.50 (br dd, 2H, J=25.8, 16.5 Hz), 3.61-3.55 (m, 1H), 3.22-3.12 (m, 2H), 2.82 (s, 3H), 2.82-2.79 (m, 1H), 2.62-2.60 (m, 1H). ESI (m/z): 232.0 (M+H). the reaction was stirred for 3 hours at room temperature and 16 hours at 70° C The reaction was cooled successively washed twice with water and once with saturated aqueous sodium chloride solutions The organic layer was dried (anhydrous sodium sulfate) filtered concentrated under reduced pressure The crude residue was purified by silica gel column chromatography (25-60% ethyl acetate in hexanes)

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Methanesulfonyl chloride (3.2 mL, 42 mmol) was slowly added to a stirring solution of furfurylamine (4.2 g, 43.2 mmol) and triethylamine (6 mL, 43 mmol) in anhydrous methylene chloride (110 mL). The reaction was stirred overnight at ambient temperature and then diluted with ethyl acetate. The organic solution was successively washed with 1N aqueous hydrochloric acid three times, saturated aqueous sodium bicarbonate and saturated aqueous sodium chloride solutions, dried (anhydrous sodium sulfate), and filtered. The solution was concentrated under reduced pressure to give the desired product as a tan liquid (6.6 g, 89%). 1H NMR (CDCl3, 300 MHz) δ 7.39-7.38 (m, 1H), 6.33-6.31 (m, 2H), 5.02 (br s, 1H), 4.33-4.31 (d, 2H, J=6 Hz). The organic solution was successively washed with 1N aqueous hydrochloric acid three times, saturated aqueous sodium bicarbonate and saturated aqueous sodium chloride solutions dried (anhydrous sodium sulfate) filtered The solution was concentrated under reduced pressure