1-chloroethyl methyl carbonate

Conditions: temp:0.00; pressure:0.00; stir:

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

Procedure: 5-Hydroxy-1-ethylpyrazol-4-yl 3-(2-methoxyethoxy)-2-methyl-4-(methylsulfonyl)phenyl ketone (300 mg) was dissolved in 2-butanone (10 mL), and potassium carbonate (130 mg) and tetrabutylammonium bromide (15 mg) were added. After stirring at room temperature for 10 minutes, 1-chloroethyl methyl carbonate (purity: 85%, 270 mg) was added at room temperature, followed by heating and refluxing for 3 hours. After completion of the reaction, the reaction mixture was cooled to room temperature and poured into water and then extracted with ethyl acetate. The organic layer was washed with 1N hydrochloric acid and a saturated sodium chloride aqueous solution, followed by drying over anhydrous sodium sulfate. The solvent was distilled off under reduced pressure. The obtained residue was purified by column chromatography with n-hexane:ethyl acetate=1:1, to obtain the desired product (180 mg) as slightly yellow solid. The NMR spectrum data of this product are as follows. by heating refluxing for 3 hours After completion of the reaction the reaction mixture was cooled to room temperature extracted with ethyl acetate The organic layer was washed with 1N hydrochloric acid by drying over anhydrous sodium sulfate The solvent was distilled off under reduced pressure The obtained residue was purified by column chromatography with n-hexane

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

Procedure: 5-Hydroxy-1-ethylpyrazol-4-yl 3-(2-methoxyethoxy)-2-methyl-4-(methylsulfonyl)phenyl ketone (300 mg) was dissolved in 2-butanone (10 mL), and potassium carbonate (130 mg) and tetrabutylammonium bromide (15 mg) were added. After stirring at room temperature for 10 minutes, 1-chloroethyl methyl carbonate (purity: 85%, 270 mg) was added at room temperature, followed by heating and refluxing for 3 hours. After completion of the reaction, the reaction mixture was cooled to room temperature and poured into water and then extracted with ethyl acetate. The organic layer was washed with 1N hydrochloric acid and a saturated sodium chloride aqueous solution, followed by drying over anhydrous sodium sulfate. The solvent was distilled off under reduced pressure. The obtained residue was purified by column chromatography with n-hexane:ethyl acetate=1:1, to obtain the desired product (180 mg) as slightly yellow solid. The NMR spectrum data of this product are as follows. by heating refluxing for 3 hours After completion of the reaction the reaction mixture was cooled to room temperature extracted with ethyl acetate The organic layer was washed with 1N hydrochloric acid by drying over anhydrous sodium sulfate The solvent was distilled off under reduced pressure The obtained residue was purified by column chromatography with n-hexane

Conditions: temp:0.00; pressure:0.00; stir:

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

Procedure: 5-Hydroxy-1-ethylpyrazol-4-yl 3-(2-methoxyethoxy)-2-methyl-4-(methylsulfonyl)phenyl ketone (300 mg) was dissolved in 2-butanone (10 mL), and potassium carbonate (130 mg) and tetrabutylammonium bromide (15 mg) were added. After stirring at room temperature for 10 minutes, 1-chloroethyl methyl carbonate (purity: 85%, 270 mg) was added at room temperature, followed by heating and refluxing for 3 hours. After completion of the reaction, the reaction mixture was cooled to room temperature and poured into water and then extracted with ethyl acetate. The organic layer was washed with 1N hydrochloric acid and a saturated sodium chloride aqueous solution, followed by drying over anhydrous sodium sulfate. The solvent was distilled off under reduced pressure. The obtained residue was purified by column chromatography with n-hexane:ethyl acetate=1:1, to obtain the desired product (180 mg) as slightly yellow solid. The NMR spectrum data of this product are as follows. 1H=NMR δppm (measuring instrument: JEOL-GSX (400 MHz), solvent: CDCl3) 1.40 (3H, t, J=7.2 Hz), 1.77 (3H, d, J=5.2 Hz), 2.35 (3H, s), 2.94 (3H, s), 3.46 (3H, s), 3.71 (3H, s), 3.80 (2H, t, J=4.4 Hz), 4.05 (2H, m), 4.24 (2H, t, J=4.4 Hz), 6.78 (1H, q, J=5.2 Hz), 7.26 (1H, d, J=7.6 Hz), 7.28 (1H, s), 7.88 (1H, d, J=7.6 Hz). by heating refluxing for 3 hours After completion of the reaction the reaction mixture was cooled to room temperature extracted with ethyl acetate The organic layer was washed with 1N hydrochloric acid by drying over anhydrous sodium sulfate The solvent was distilled off under reduced pressure The obtained residue was purified by column chromatography with n-hexane

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

Procedure: By the method of Example 6, using a reflux time of 1 hour prior to addition of a sodium iodide, piroxicam (2.00 g, 6.0 mmol) and alpha-chloroethyl methyl carbonate (2.50 g, 18.1 mmol) were converted to chromatographed title product as a yellow solid which was crystallized from isopropyl alcohol (660 mg, 1.5 mmol, 25.0%): mp 150°-151° C.; IR (KBr) 1757, 1677 cm-1 ; 1H NMR (CDCl3) delta 1.75 (d, J=6 Hz, 3H), 3.12 (s, 3H), 3.65 (s, 3H), 6.35 (q, J=6 Hz, 1H), 7.07-7.18 (m, 1H), 7.65-7.95 (m, 5H), 8.30-8.42 (m, 2H), 9.42 (br s, 1H); precise mass calcd for C19H19N3O7S m/e 433.0944, found 433.1004. a reflux time of 1 hour to chromatographed title product as a yellow solid which

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

Procedure: Potassium tert. butoxide (3.70 g, 0.033 mol ) was added to a solution of methacrylic acid (2.84 g, 0.033 mol) in DMF (100 ml). Methyl 1-chloroethyl carbonate (4.55 g, 0.033 mol) from Example 1u(i) above was added to the resulting suspension. 18-crown-6 (0.61 g, 2.3 mmol) was then added and the reaction mixture was left with stirring at room temperature for 3 days. The reaction mixture was filtered and the solvent was removed under reduced pressure. The residue was dissolved in chloroform (100 ml) and washed with saturated aqueous sodium hydrogen carbonate (50 ml) and water (50 ml). The organic phase was dried (MgSO4) and the solvent removed under reduced pressure. Flash chromatography gave 4.46 g (72%) of the title product. the reaction mixture was left The reaction mixture was filtered the solvent was removed under reduced pressure The residue was dissolved in chloroform (100 ml) washed with saturated aqueous sodium hydrogen carbonate (50 ml) and water (50 ml) The organic phase was dried (MgSO4) the solvent removed under reduced pressure

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

Procedure: 5-Hydroxy-1,3-dimethylpyrazol-4-yl 3-(2-methoxyethoxy)-2-methyl-4-(methylsulfonyl)phenyl ketone (300 mg) was dissolved in 2-butanone (10 mL), and potassium carbonate (130 mg) and tetrabutyl ammonium bromide (15 mg) were added. After stirring at room temperature for 10 minutes, 1-chloroethyl methyl carbonate (purity: 85%, 270 mg) was added at room temperature, followed by heating and refluxing for 3 hours. After completion of the reaction, the reaction solution was cooled to room temperature and poured into water and then extracted with ethyl acetate. The organic layer was washed with a 1N hydrochloric solution and a saturated sodium chloride aqueous solution and then dried over anhydrous sodium sulfate. The solvent was distilled off under reduced pressure. The obtained residue was purified by column chromatography (n-hexane:ethyl acetate=1:1) to obtain the desired product (200 mg) as slightly yellow solid. by heating refluxing for 3 hours After completion of the reaction the reaction solution was cooled to room temperature extracted with ethyl acetate The organic layer was washed with a 1N hydrochloric solution a saturated sodium chloride aqueous solution and then dried over anhydrous sodium sulfate The solvent was distilled off under reduced pressure The obtained residue was purified by column chromatography (n-hexane:ethyl acetate=1:1)

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

Procedure: 5-Hydroxy-1-ethylpyrazol-4-yl 3-(2-methoxyethoxy)-2-methyl-4-(methylsulfonyl)phenyl ketone (300 mg) was dissolved in 2-butanone (10 mL), and potassium carbonate (130 mg) and tetrabutylammonium bromide (15 mg) were added. After stirring at room temperature for 10 minutes, 1-chloroethyl methyl carbonate (purity: 85%, 270 mg) was added at room temperature, followed by heating and refluxing for 3 hours. After completion of the reaction, the reaction mixture was cooled to room temperature and poured into water and then extracted with ethyl acetate. The organic layer was washed with 1N hydrochloric acid and a saturated sodium chloride aqueous solution, followed by drying over anhydrous sodium sulfate. The solvent was distilled off under reduced pressure. The obtained residue was purified by column chromatography with n-hexane:ethyl acetate=1:1, to obtain the desired product (180 mg) as slightly yellow solid. by heating refluxing for 3 hours After completion of the reaction the reaction mixture was cooled to room temperature extracted with ethyl acetate The organic layer was washed with 1N hydrochloric acid by drying over anhydrous sodium sulfate The solvent was distilled off under reduced pressure The obtained residue was purified by column chromatography with n-hexane

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

Procedure: 5-Hydroxy-1-ethylpyrazol-4-yl 3-(2-methoxyethoxy)-2-methyl-4-(methylsulfonyl)phenyl ketone (300 mg) was dissolved in 2-butanone (10 mL), and potassium carbonate (130 mg) and tetrabutylammonium bromide (15 mg) were added. After stirring at room temperature for 10 minutes, 1-chloroethyl methyl carbonate (purity: 85%, 270 mg) was added at room temperature, followed by heating and refluxing for 3 hours. After completion of the reaction, the reaction mixture was cooled to room temperature and poured into water and then extracted with ethyl acetate. The organic layer was washed with 1N hydrochloric acid and a saturated sodium chloride aqueous solution, followed by drying over anhydrous sodium sulfate. The solvent was distilled off under reduced pressure. The obtained residue was purified by column chromatography with n-hexane:ethyl acetate=1:1, to obtain the desired product (180 mg) as slightly yellow solid. The NMR spectrum data of this product are as follows. by heating refluxing for 3 hours After completion of the reaction the reaction mixture was cooled to room temperature extracted with ethyl acetate The organic layer was washed with 1N hydrochloric acid by drying over anhydrous sodium sulfate The solvent was distilled off under reduced pressure The obtained residue was purified by column chromatography with n-hexane