1,3-DIHYDRO-2,1-BENZISOTHIAZOLE 2,2-DIOXIDE

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

Procedure: A mixture of 1,3-dihydro-2,1-benzisothiazole 2,2-dioxide (J. Heterocyclic Chem. 1986, 23, 1645., 401 mg, 2.37 mmol), methyl iodide (0.6 mL, 9.48 mmol) and potassium carbonate (328 mg, 2.37 mmol) in N,N-dimethylformamide (7 mL) was stirred for 4 h at room temperature. The reaction mixture was diluted with toluene/ethyl acetate (1/3), then washed with water for two times, and then the organic layer washed with brine, dried over sodium sulfate, and evaporated. The residue was purified by preparative thin layer chromatography on silica gel developing with hexane/ethyl acetate (2/1) to afford 272 mg (63%) of the title compound as a slight brown syrup: washed with water for two times the organic layer washed with brine dried over sodium sulfate evaporated The residue was purified by preparative thin layer chromatography on silica gel developing with hexane/ethyl acetate (2/1)

Conditions: temp:70.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: The title compound was prepared using the method described in WO 98/32438 A1. To a solution of 2-nitro-alpha-toluenesulfonyl chloride (5.1 g, 21.6 mmol) in anhydrous ethyl acetate (250 mL) was added tin (II) chloride (19.3 g, 86 mmol). The reaction was stirred overnight at 70° C., then poured onto ice and neutralized with saturated aqueous sodium bicarbonate. The solution was filtered through Celite, extracted with ethyl acetate, and the organic layer concentrated. To the crude residue was added anhydrous methylene chloride (200 mL) and triethylamine (5 mL). The solution was stirred overnight at room temperature and concentrated under reduced pressure. The product was obtained by silica gel column chromatography (30-100% ethyl acetate in hexanes) followed by recrystallization from methylene chloride/hexanes to give a white solid. (0.24 g, 6.5%). 1H NMR (CDCl3, 300 MHz) δ 7.30-7.22 (m, 2H), 7.07-7.02 (t, 1H, J=7.4 Hz), 6.89-6.86 (dd, 1H, J=0.6, 8.1 Hz), 6.66 (br s, 1H), 4.39 (s, 1H). The solution was filtered through Celite extracted with ethyl acetate the organic layer concentrated To the crude residue was added anhydrous methylene chloride (200 mL) and triethylamine (5 mL) The solution was stirred overnight at room temperature concentrated under reduced pressure The product was obtained by silica gel column chromatography (30-100% ethyl acetate in hexanes) followed by recrystallization from methylene chloride/hexanes to give a white solid

Conditions: temp:2.51; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A solution of allyl (1S,5R,6S)-6-[1(R)-allyloxycarbonyloxyethyl]-2-hydroxymethyl-1-methyl-carbapen-2-em-3-carboxylate (25.5 mg, 0.07 mmol), 1,3-dihydro-benzo[c]isothiazole 2,2-dioxide (13 mg, 0.077 mmol), and triphenylphosphine (28 mg, 0.105 mmol) in anhydrous tetrahydrofuran (0.4 mL) was cooled in an ice bath and treated with diethyl azodicarboxylate (0.017 mL, 0.105 mmol). The mixture was stirred at 0-5° C. for 30 minutes, then streaked onto a 1 mm×20 cm×20 cm silica gel GF plates. The plates were developed with 5% ethyl acetate in dichloromethane. The product band was removed and eluted with ethyl acetate to afford allyl (1S,5R,6S)-6-[1(R)-allyloxycarbonyloxy-ethyl]-2-(2,2-dioxo-2,3-dihydro-benzo [c]isothiazol-1-yl-methyl)-1-methyl-carbapen-2-em-3-carboxylate (15 mg) as an oil. The product band was removed eluted with ethyl acetate

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

Procedure: A mixture of 1,3-dihydro-2,1-benzisothiazole 2,2-dioxide (J. Heterocyclic Chem. 1986, 23, 1645., 401 mg, 2.37 mmol), methyl iodide (0.6 mL, 9.48 mmol) and potassium carbonate (328 mg, 2.37 mmol) in N,N-dimethylformamide (7 mL) was stirred for 4 h at room temperature. The reaction mixture was diluted with toluene/ethyl acetate (1/3), then washed with water for two times, and then the organic layer was washed with brine, dried over sodium sulfate, and evaporated. The residue was purified by preparative thin layer chromatography on silica gel developing with hexane/ethyl acetate (2/1) to afford 272 mg (63%) of the title compound as a slight brown syrup: washed with water for two times the organic layer was washed with brine dried over sodium sulfate evaporated The residue was purified by preparative thin layer chromatography on silica gel developing with hexane/ethyl acetate (2/1)

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

Procedure: A mixture of 1,3-dihydro-2,1-benzisothiazole 2,2-dioxide (J. Heterocyclic Chem. 1986, 23, 1645., 401 mg, 2.37 mmol), methyl iodide (0.6 mL, 9.48 mmol) and potassium carbonate (328 mg, 2.37 mmol) in N,N-dimethylformamide (7 mL) was stirred for 4 h at room temperature. The reaction mixture was diluted with toluene/ethyl acetate (1/3), then washed with water for two times, and then the organic layer washed with brine, dried over sodium sulfate, and evaporated. The residue was purified by preparative thin layer chromatography on silica gel developing with hexane/ethyl acetate (2/1) to afford 272 mg (63%) of the title compound as a slight brown syrup: washed with water for two times the organic layer washed with brine dried over sodium sulfate evaporated The residue was purified by preparative thin layer chromatography on silica gel developing with hexane/ethyl acetate (2/1)