(4S,5S)-4,5-dimethyl-1,3,2-dioxathiolane 2,2-dioxide

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

Procedure: To a solution of 5-(2-chloro-4-fluorophenyl)-4-methyl-N-[4-(methylsulfonyl)phenyl]-1H-pyrrole-3-carboxamide (0.50 g, 1.2 mmol) in anhydrous DMA (8.0 ml) was added sodium tert-butoxide (0.27 g, 2.8 mmol) and stirred at room temperature for 30 min under N2. (4S,5S)-4,5-dimethyl-1,3,2-dioxathiolane 2,2-dioxide (0.28 g, 1.8 mmol) in anhydrous DMA (2.0 ml) was added to the solution and stirred at 70° C. for 2.0 h. The reaction mixture was cooled to room temperature and added 2N HCl (2.0 ml) and concentrated on a rotary evaporator. To this residue was added anhydrous THF (4.0 ml) and 5N HCl (5.0 ml) and stirred at 60° C. for 80 min. The mixture was diluted with ethyl acetate and washed with water, satd NaHCO3 and brine, then dried over sodium sulfate and concentrated on a rotary evaporator. The resulting residue was purified by silica-gel column chromatography (3:7 to 2:8 hexane:ethyl acetate) to give an atropisomeric mixture of the title compound (0.29 g, 50%) as a white solid. stirred at 70° C. for 2.0 h The reaction mixture was cooled to room temperature concentrated on a rotary evaporator To this residue was added anhydrous THF (4.0 ml) and 5N HCl (5.0 ml) stirred at 60° C. for 80 min The mixture was diluted with ethyl acetate washed with water dried over sodium sulfate concentrated on a rotary evaporator The resulting residue was purified by silica-gel column chromatography (3:7 to 2:8 hexane:ethyl acetate) to give

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

Procedure: To a solution of 5-[4-chloro-2-(trifluoromethyl)phenyl]-4-methyl-N-[4-(methylsulfonyl)phenyl]-1H-pyrrole-3-carboxamide (21 g, 47 mmol) in anhydrous DMA (234 ml) was added sodium tert-butoxide (10 g, 0.11 mol) and stirred at room temperature for 30 min under N2. (4S,5S)-4,5-dimethyl-1,3,2-dioxathiolane 2,2-dioxide (11 g, 70 mmol) in anhydrous DMA (50 ml) was added to the solution and stirred at 70° C. for 2.0 h. The reaction mixture was cooled to 0° C. and added 2N HCl (100 ml) and concentrated on a rotary evaporator. To this residue was added anhydrous THF (120 ml) and 5N HCl (120 ml) and stirred at 60° C. for 90 min. The mixture was diluted with ethyl acetate and washed with water, satd NaHCO3 and brine, then dried over sodium sulfate and concentrated on a rotary evaporator. The resulting residue was purified by silica-gel column chromatography (1:1 to 1:9 hexane:ethyl acetate) to give an atropisomeric mixture of the title compound (10.9 g, 44%) as a white solid. stirred at 70° C. for 2.0 h The reaction mixture was cooled to 0° C. concentrated on a rotary evaporator To this residue was added anhydrous THF (120 ml) and 5N HCl (120 ml) stirred at 60° C. for 90 min The mixture was diluted with ethyl acetate washed with water dried over sodium sulfate concentrated on a rotary evaporator The resulting residue was purified by silica-gel column chromatography (1:1 to 1:9 hexane:ethyl acetate) to give

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

Procedure: To a solution of 5-[4-chloro-2-(trifluoromethyl)phenyl]-4-methyl-N-[4-(methylsulfonyl)phenyl]-1H-pyrrole-3-carboxamide (21 g, 47 mmol) in anhydrous DMA (234 ml) was added sodium tert-butoxide (10 g, 0.11 mol) and stirred at room temperature for 30 min under N2. (4S,5S)-4,5-dimethyl-1,3,2-dioxathiolane 2,2-dioxide (11 g, 70 mmol) in anhydrous DMA (50 ml) was added to the solution and stirred at 70° C. for 2.0 h. The reaction mixture was cooled to 0° C. and added 2N HCl (100 ml) and concentrated on a rotary evaporator. To this residue was added anhydrous THF (120 ml) and 5N HCl (120 ml) and stirred at 60° C. for 90 min. The mixture was diluted with ethyl acetate and washed with water, satd NaHCO3 and brine, then dried over sodium sulfate and concentrated on a rotary evaporator. The resulting residue was purified by silica-gel column chromatography (1:1 to 1:9 hexane:ethyl acetate) to give an atropisomeric mixture of the title compound (10.9 g, 44%) as a white solid. stirred at 70° C. for 2.0 h The reaction mixture was cooled to 0° C. concentrated on a rotary evaporator To this residue was added anhydrous THF (120 ml) and 5N HCl (120 ml) stirred at 60° C. for 90 min The mixture was diluted with ethyl acetate washed with water dried over sodium sulfate concentrated on a rotary evaporator The resulting residue was purified by silica-gel column chromatography (1:1 to 1:9 hexane:ethyl acetate) to give

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

Procedure: To a solution of 5-[4-fluoro-2-(trifluoromethyl)phenyl]-4-methyl-N-[4-(methylsulfonyl)phenyl]-1H-pyrrole-3-carboxamide (23 g, 52 mmol) in anhydrous DMA (160 ml) was added sodium tert-butoxide (12 g, 0.12 mol) and stirred at room temperature for 30 min under N2. (4S,5S)-4,5-dimethyl-1,3,2-dioxathiolane 2,2-dioxide (12 g, 78 mmol) in anhydrous DMA (20 ml) was added to the solution and stirred at 70° C. for 2.0 h. The reaction mixture was cooled to room temperature and added 2N HCl (80 ml) and concentrated on a rotary evaporator. To this residue was added anhydrous THF (0.12 L) and 5N HCl (0.14 L) and stirred at 60° C. for 80 min. The mixture was diluted with ethyl acetate and washed with water, satd NaHCO3 and brine, then dried over sodium sulfate and concentrated on a rotary evaporator. The resulting residue was purified by silica-gel column chromatography (1:2, dichloromethane:ethyl acetate) to give an atropisomeric mixture of the title compound (14.3 g, 52%) as a pale yellow solid. stirred at 70° C. for 2.0 h The reaction mixture was cooled to room temperature concentrated on a rotary evaporator To this residue was added anhydrous THF (0.12 L) and 5N HCl (0.14 L) stirred at 60° C. for 80 min The mixture was diluted with ethyl acetate washed with water dried over sodium sulfate concentrated on a rotary evaporator The resulting residue was purified by silica-gel column chromatography (1:2, dichloromethane:ethyl acetate) to give

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

Procedure: To a solution of 4-methyl-N-[4-(methylsulfonyl)phenyl]-5-[2-(trifluoromethyl)phenyl]-1H-pyrrole-3-carboxamide (28 g, 66 mmol) in anhydrous N,N-dimethylacetamide (DMA) (0.53 L) was added sodium tert-butoxide (15 g, 15 mmol) and stirred at room temperature for 30 min under N2. (4S,5S)-4,5-dimethyl-1,3,2-dioxathiolane 2,2-dioxide (15 g, 99 mmol) in anhydrous DMA (2.0 ml) was added to the solution and stirred at 70° C. for 2.0 h. The reaction mixture was cooled to room temperature and added 2N HCl (0.14 L) and concentrated on a rotary evaporator. To this residue was added anhydrous tetrahydrofuran (THF) (140 ml) and 5N HCl (0.14 L) and stirred at 60° C. for 90 min. The mixture was diluted with ethyl acetate and washed with water, saturated NaHCO3 and brine, then dried over sodium sulfate and concentrated on a rotary evaporator. The resulting residue was purified by silica-gel column chromatography (9:1 to 1:1 dichloromethane:ethyl acetate) to give an atropisomeric mixture of title compound as a white solid (22.5 g, 69%). stirred at 70° C. for 2.0 h The reaction mixture was cooled to room temperature concentrated on a rotary evaporator To this residue was added anhydrous tetrahydrofuran (THF) (140 ml) and 5N HCl (0.14 L) stirred at 60° C. for 90 min The mixture was diluted with ethyl acetate washed with water, saturated NaHCO3 and brine dried over sodium sulfate concentrated on a rotary evaporator The resulting residue was purified by silica-gel column chromatography (9:1 to 1:1 dichloromethane:ethyl acetate) to give

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

Procedure: To a solution of 5-(2-chloro-4-fluorophenyl)-4-methyl-N-[4-(methylsulfonyl)phenyl]-1H-pyrrole-3-carboxamide (0.50 g, 1.2 mmol) in anhydrous DMA (8.0 ml) was added sodium tert-butoxide (0.27 g, 2.8 mmol) and stirred at room temperature for 30 min under N2. (4S,5S)-4,5-dimethyl-1,3,2-dioxathiolane 2,2-dioxide (0.28 g, 1.8 mmol) in anhydrous DMA (2.0 ml) was added to the solution and stirred at 70° C. for 2.0 h. The reaction mixture was cooled to room temperature and added 2N HCl (2.0 ml) and concentrated on a rotary evaporator. To this residue was added anhydrous THF (4.0 ml) and 5N HCl (5.0 ml) and stirred at 60° C. for 80 min. The mixture was diluted with ethyl acetate and washed with water, satd NaHCO3 and brine, then dried over sodium sulfate and concentrated on a rotary evaporator. The resulting residue was purified by silica-gel column chromatography (3:7 to 2:8 hexane:ethyl acetate) to give an atropisomeric mixture of the title compound (0.29 g, 50%) as a white solid. stirred at 70° C. for 2.0 h The reaction mixture was cooled to room temperature concentrated on a rotary evaporator To this residue was added anhydrous THF (4.0 ml) and 5N HCl (5.0 ml) stirred at 60° C. for 80 min The mixture was diluted with ethyl acetate washed with water dried over sodium sulfate concentrated on a rotary evaporator The resulting residue was purified by silica-gel column chromatography (3:7 to 2:8 hexane:ethyl acetate) to give

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

Procedure: To a solution of 5-[4-chloro-2-(trifluoromethyl)phenyl]-4-methyl-N-[4-(methylsulfonyl)phenyl]-1H-pyrrole-3-carboxamide (21 g, 47 mmol) in anhydrous DMA (234 ml) was added sodium tert-butoxide (10 g, 0.11 mol) and stirred at room temperature for 30 min under N2. (4S,5S)-4,5-dimethyl-1,3,2-dioxathiolane 2,2-dioxide (11 g, 70 mmol) in anhydrous DMA (50 ml) was added to the solution and stirred at 70° C. for 2.0 h. The reaction mixture was cooled to 0° C. and added 2N HCl (100 ml) and concentrated on a rotary evaporator. To this residue was added anhydrous THF (120 ml) and 5N HCl (120 ml) and stirred at 60° C. for 90 min. The mixture was diluted with ethyl acetate and washed with water, satd NaHCO3 and brine, then dried over sodium sulfate and concentrated on a rotary evaporator. The resulting residue was purified by silica-gel column chromatography (1:1 to 1:9 hexane:ethyl acetate) to give an atropisomeric mixture of the title compound (10.9 g, 44%) as a white solid. stirred at 70° C. for 2.0 h The reaction mixture was cooled to 0° C. concentrated on a rotary evaporator To this residue was added anhydrous THF (120 ml) and 5N HCl (120 ml) stirred at 60° C. for 90 min The mixture was diluted with ethyl acetate washed with water dried over sodium sulfate concentrated on a rotary evaporator The resulting residue was purified by silica-gel column chromatography (1:1 to 1:9 hexane:ethyl acetate) to give

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

Procedure: To a solution of 5-[4-fluoro-2-(trifluoromethyl)phenyl]-4-methyl-N-[4-(methylsulfonyl)phenyl]-1H-pyrrole-3-carboxamide (23 g, 52 mmol) in anhydrous DMA (160 ml) was added sodium tert-butoxide (12 g, 0.12 mol) and stirred at room temperature for 30 min under N2. (4S,5S)-4,5-dimethyl-1,3,2-dioxathiolane 2,2-dioxide (12 g, 78 mmol) in anhydrous DMA (20 ml) was added to the solution and stirred at 70° C. for 2.0 h. The reaction mixture was cooled to room temperature and added 2N HCl (80 ml) and concentrated on a rotary evaporator. To this residue was added anhydrous THF (0.12 L) and 5N HCl (0.14 L) and stirred at 60° C. for 80 min. The mixture was diluted with ethyl acetate and washed with water, satd NaHCO3 and brine, then dried over sodium sulfate and concentrated on a rotary evaporator. The resulting residue was purified by silica-gel column chromatography (1:2, dichloromethane:ethyl acetate) to give an atropisomeric mixture of the title compound (14.3 g, 52%) as a pale yellow solid. stirred at 70° C. for 2.0 h The reaction mixture was cooled to room temperature concentrated on a rotary evaporator To this residue was added anhydrous THF (0.12 L) and 5N HCl (0.14 L) stirred at 60° C. for 80 min The mixture was diluted with ethyl acetate washed with water dried over sodium sulfate concentrated on a rotary evaporator The resulting residue was purified by silica-gel column chromatography (1:2, dichloromethane:ethyl acetate) to give

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

Procedure: To a solution of 4-methyl-N-[4-(methylsulfonyl)phenyl]-5-[2-(trifluoromethyl)phenyl]-1H-pyrrole-3-carboxamide (28 g, 66 mmol) in anhydrous N,N-dimethylacetamide (DMA) (0.53 L) was added sodium tert-butoxide (15 g, 15 mmol) and stirred at room temperature for 30 min under N2. (4S,5S)-4,5-dimethyl-1,3,2-dioxathiolane 2,2-dioxide (15 g, 99 mmol) in anhydrous DMA (2.0 ml) was added to the solution and stirred at 70° C. for 2.0 h. The reaction mixture was cooled to room temperature and added 2N HCl (0.14 L) and concentrated on a rotary evaporator. To this residue was added anhydrous tetrahydrofuran (THF) (140 ml) and 5N HCl (0.14 L) and stirred at 60° C. for 90 min. The mixture was diluted with ethyl acetate and washed with water, saturated NaHCO3 and brine, then dried over sodium sulfate and concentrated on a rotary evaporator. The resulting residue was purified by silica-gel column chromatography (9:1 to 1:1 dichloromethane:ethyl acetate) to give an atropisomeric mixture of title compound as a white solid (22.5 g, 69%). stirred at 70° C. for 2.0 h The reaction mixture was cooled to room temperature concentrated on a rotary evaporator To this residue was added anhydrous tetrahydrofuran (THF) (140 ml) and 5N HCl (0.14 L) stirred at 60° C. for 90 min The mixture was diluted with ethyl acetate washed with water, saturated NaHCO3 and brine dried over sodium sulfate concentrated on a rotary evaporator The resulting residue was purified by silica-gel column chromatography (9:1 to 1:1 dichloromethane:ethyl acetate) to give