calcium;dihypochlorite

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

Procedure: To a solution of calcium hypochlorite (29.4 g, 137.8 mmol) in water:acetic acid (125:9.5) was added a solution of 8-difluoromethoxychroman-4-one (7.4 g, 34.6 mmol, see step (iv) above) in acetonitrile (20 mL), whereafter the reaction mixture was stirred overnight. The mixture was diluted with water and extracted with ether (3×) and with EtOAc (1×). The combined organic layers were washed with water (3×), dried (Na2SO4) and evaporated, yielding 8.0 g (93%) of the subtitle compound. extracted with ether (3×) and with EtOAc (1×) The combined organic layers were washed with water (3×) dried (Na2SO4) evaporated

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

Procedure: To a solution of calcium hypochlorite (15.4 g, 72.4 mmol) in water:acetic acid (65:5) was added a solution of 8-trifluoromethoxychroman-4-one (4.2 g, 18.1 mmol; from step (iv) above) in acetonitrile (20 mL), whereafter the reaction mixture was stirred overnight. The mixture was diluted with water and extracted with ether (3 times) and EtOAc (once). The combined organic layer was washed with water, dried (Na2SO4) and evaporated, yielding 4.2 g (87%) of the sub-tide compound. extracted with ether (3 times) and EtOAc (once) The combined organic layer was washed with water dried (Na2SO4) evaporated

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

Procedure: In 10 ml of dichloromethane, 1.0 g (5.0 mmol) of 5-(1-hydroxypropyl)-3-phenylisoxazole was dissolved. To the solution were added 100 mg (0.9 mmol) of pyridine hydrochloride, followed by the further addition of 1.4 g (9.9 mmol) of calcium hypochlorite. They were reacted at room temperature for 5 hours. After completion of the reaction, insoluble matter was filtered off and the organic layer was washed with water. The organic layer was dried over anhydrous sodium sulfate and the solvent was distilled off under reduced pressure. The residue was then recrystallized from ethanol, whereby the target compound, namely, 5-propionyl-3-phenylisoxazole was obtained as crystals. They were reacted at room temperature for 5 hours After completion of the reaction, insoluble matter was filtered off the organic layer was washed with water The organic layer was dried over anhydrous sodium sulfate the solvent was distilled off under reduced pressure The residue was then recrystallized from ethanol, whereby the target compound

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

Procedure: Acetic anhydride (152 mL, 1.6 moles) was added dropwise to a rapidly stirring mixture of 4-aminophenylacetic acid (195 grams, 1.3 moles) in acetic acid (600 mL) and water (250 mL) at room temperature. After a slight exotherm, the dark brown solution was stirred for one hour at room temperature. The solution was diluted with ethanol (500 mL) and water (250 mL), and a suspension of Calcium hypochlorite (340 grams, 2.3 moles) in water (1L plus 500 mL rinse) was added portionwise. The temperature rose to 50° C. and the mixture was stirred for 16 hours at room temperature. The mixture was poured into ice-water (8 L) and extracted with ethyl acetate (3×2 L). The combined extracts were washed with saturated brine, dried over magnesium sulfate and concentrated in vacuo to a small volume. Hexane was added and the resulting precipitate filtered, washed with hexane and dried to give the title compound(180 grams) as a brown solid After a slight exotherm, the dark brown solution was stirred for one hour at room temperature was added portionwise rose to 50° C. the mixture was stirred for 16 hours at room temperature extracted with ethyl acetate (3×2 L) The combined extracts were washed with saturated brine dried over magnesium sulfate concentrated in vacuo to a small volume Hexane was added the resulting precipitate filtered washed with hexane dried

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

Procedure: Sodium bicarbonate (8.81 g, 0.105 mol) was added to a solution of 15.0 g (0.075 mol) of 3,3-dimethyl-1,5-dioxaspiro<5.5>undecan-9-ol in 150 ml of acetonitrile. The reaction mixture was charged with 15.0 g of silica gel (MCB 60-200 mesh) and 15.0 g of calcium hypochlorite in sequence. The reaction mixture was stirred at a temperature in the range of 24° C. to 28° C. for about 18 hours and then warmed to 29° C. to 30° C. for 4 hours. The mixture was filtered and evaporated under vacuum. The residue was combined with 135 ml of toluene and 50 ml of water, and the resulting mixture was stirred for 45 minutes. The organic phase was separated, washed with 50 ml of a saturated sodium chloride solution and dried over 10.0 g of anhydrous sodium sulfate. A gas chromatograph of the sample showed 93.6% pure product. The organic phase was concentrated under vacuum to afford 13.97 g of 3,3-dimethyl-1,5-dioxaspiro<5.5>undecan-9-one. warmed to 29° C. to 30° C. for 4 hours The mixture was filtered evaporated under vacuum the resulting mixture was stirred for 45 minutes The organic phase was separated washed with 50 ml of a saturated sodium chloride solution dried over 10.0 g of anhydrous sodium sulfate The organic phase was concentrated under vacuum

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

Procedure: Sodium bicarbonate (8.81 g, 0.105 mol) was added to a solution of 15.0 g (0.075 mol) of 3,3-dimethyl-1,5-dioxaspiro<5.5>undecan-9-ol in 150 ml of acetonitrile. The reaction mixture was charged with 15.0 g of silica gel (MCB 60-200 mesh) and 15.0 g of calcium hypochlorite in sequence. The reaction mixture was stirred at a temperature in the range of 24° C. to 28° C. for about 18 hours and then warmed to 29° C. to 30° C. for 4 hours. The mixture was filtered and evaporated under vacuum. The residue was combined with 135 ml of toluene and 50 ml of water, and the resulting mixture was stirred for 45 minutes. The organic phase was separated, washed with 50 ml of a saturated sodium chloride solution and dried over 10.0 g of anhydrous sodium sulfate. A gas chromatograph of the sample showed 93.6% pure product. The organic phase was concentrated under vacuum to afford 13.97 g of 3,3-dimethyl-1,5-dioxaspiro<5.5>undecan-9-one. warmed to 29° C. to 30° C. for 4 hours The mixture was filtered evaporated under vacuum the resulting mixture was stirred for 45 minutes The organic phase was separated washed with 50 ml of a saturated sodium chloride solution dried over 10.0 g of anhydrous sodium sulfate The organic phase was concentrated under vacuum

Conditions: temp:28.51; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Forty grams (0.2 mol) of 3,3-dimethyl-1,5-dioxaspiro<5.5>undecan-9-ol were dissolved in 400 ml of acetonitrile, and 23.5 g of sodium bicarbonate was added thereto with stirring. Next, 40.0 g of silica gel (MCB Grade 62 60-200 mesh) was added to the mixture, which was followed by the addition of 40.0 g (0.28 mol) of calcium hypochlorite (Fisher Chemical Company) portionwise over a period of 90 seconds. The reaction mixture was stirred at 23.5° C. for one hour and then heated slowly to 28.5° C., and the reaction mixture was stirred overnight. The mixture was filtered into a stirring solution of 8.0 g of sodium bicarbonate in 80 ml of water. The flask was rinsed with 200 ml of toluene and the filtrate was stirred for 90 minutes. The mixture was partially evaporated under reduced pressure and 400 ml of toluene was added thereto. The organic phase was washed with 100 ml of a saturated aqueous sodium chloride solution containing 5.0 g of sodium bicarbonate. The organic phase was dried over anhydrous sodium sulfate. The volatiles were removed under reduced pressure and the residue was held under vacuum for about 60 hours. A total of 38.56 g of 3,3-dimethyl-1,5-dioxaspiro<5.5>-undecan-9-one was obtained having a purity of 93.7% by gas chromatographic analysis (97.2% crude yield). The compound was stored in a solution of 3.55 g of sodium bicarbonate in 200 ml methylene chloride in a sealed bottle. Next, 40.0 g of silica gel (MCB Grade 62 60-200 mesh) was added to the mixture, which The reaction mixture was stirred at 23.5° C. for one hour the reaction mixture was stirred overnight The mixture was filtered into a stirring solution of 8.0 g of sodium bicarbonate in 80 ml of water The flask was rinsed with 200 ml of toluene the filtrate was stirred for 90 minutes The mixture was partially evaporated under reduced pressure and 400 ml of toluene was added The organic phase was washed with 100 ml of a saturated aqueous sodium chloride solution containing 5.0 g of sodium bicarbonate The organic phase was dried over anhydrous sodium sulfate The volatiles were removed under reduced pressure

Conditions: temp:28.51; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Forty grams (0.2 mol) of 3,3-dimethyl-1,5-dioxaspiro<5.5>undecan-9-ol were dissolved in 400 ml of acetonitrile, and 23.5 g of sodium bicarbonate was added thereto with stirring. Next, 40.0 g of silica gel (MCB Grade 62 60-200 mesh) was added to the mixture, which was followed by the addition of 40.0 g (0.28 mol) of calcium hypochlorite (Fisher Chemical Company) portionwise over a period of 90 seconds. The reaction mixture was stirred at 23.5° C. for one hour and then heated slowly to 28.5° C., and the reaction mixture was stirred overnight. The mixture was filtered into a stirring solution of 8.0 g of sodium bicarbonate in 80 ml of water. The flask was rinsed with 200 ml of toluene and the filtrate was stirred for 90 minutes. The mixture was partially evaporated under reduced pressure and 400 ml of toluene was added thereto. The organic phase was washed with 100 ml of a saturated aqueous sodium chloride solution containing 5.0 g of sodium bicarbonate. The organic phase was dried over anhydrous sodium sulfate. The volatiles were removed under reduced pressure and the residue was held under vacuum for about 60 hours. A total of 38.56 g of 3,3-dimethyl-1,5-dioxaspiro<5.5>-undecan-9-one was obtained having a purity of 93.7% by gas chromatographic analysis (97.2% crude yield). The compound was stored in a solution of 3.55 g of sodium bicarbonate in 200 ml methylene chloride in a sealed bottle. Next, 40.0 g of silica gel (MCB Grade 62 60-200 mesh) was added to the mixture, which The reaction mixture was stirred at 23.5° C. for one hour the reaction mixture was stirred overnight The mixture was filtered into a stirring solution of 8.0 g of sodium bicarbonate in 80 ml of water The flask was rinsed with 200 ml of toluene the filtrate was stirred for 90 minutes The mixture was partially evaporated under reduced pressure and 400 ml of toluene was added The organic phase was washed with 100 ml of a saturated aqueous sodium chloride solution containing 5.0 g of sodium bicarbonate The organic phase was dried over anhydrous sodium sulfate The volatiles were removed under reduced pressure

Conditions: temp:-5.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Acetonitrile (50 mL), cyanamide (1.14 grams, 27.1 mmoles) and 3-[1-(methylthio)ethyl]-6-(trifluoromethyl)pyridine (5.00 grams, 22.6 mmoles, 99+% assay) were combined in a 100 mL, 3-necked round bottom flask equipped with a thermowell/K-thermocouple, stopper, nitrogen oil bubbler and magnetic stir bar. The stirred solution was cooled to about −5° C. with an acetone/ice bath. To this solution was added 55.96 grams of an aqueous 6.0 wt % calcium hypochlorite solution (3.36 grams of calcium hypochlorite, 23.5 mmoles, 65% available chlorine) dropwise over 44 minutes. Some undissolved solids were present in the calcium hypochlorite solution and were added as well. The temperature was kept below 0° C. during the addition. The pale yellow reaction mixture was allowed to stir at about 0° C. for 65 minutes. To the yellow reaction mixture was added 0.53 g (2.8 mmoles) of sodium metabisulfite, in portions as a solid to destroy any remaining oxidant. A white flocculant was present in the reaction mixture. It was removed by vacuum filtration of the entire reaction mixture through a medium sintered glass filter funnel. The filtrate was transferred to a separatory funnel and the phases were allowed to settle. The phases were separated and the aqueous phase re-extracted with acetonitrile (10 mL) and (15 mL). Sodium chloride (10.01 grams) was added to the aqueous phase during the second extraction to facilitate a phase break. The organics were combined and this acetonitrile/sulfilimine solution was used directly in the following oxidation. LC analysis indicated a 1.00:1.08 area ratio of the two sulfilimine isomers and showed sulfilimine at 80 area % and sulfoxide (two isomers) at 13 area %. equipped with a thermowell/K-thermocouple, stopper, nitrogen oil bubbler and magnetic stir bar were added as well The temperature was kept below 0° C. during the addition in portions as a solid to destroy any remaining oxidant It was removed by vacuum filtration of the entire reaction mixture through a medium sintered glass filter funnel The filtrate was transferred to a separatory funnel The phases were separated the aqueous phase re-extracted with acetonitrile (10 mL) and (15 mL) Sodium chloride (10.01 grams) was added to the aqueous phase during the second extraction

Conditions: temp:-5.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Acetonitrile (50 mL), cyanamide (1.14 grams, 27.1 mmoles) and 3-[1-(methylthio)ethyl]-6-(trifluoromethyl)pyridine (5.00 grams, 22.6 mmoles, 99+% assay) were combined in a 100 mL, 3-necked round bottom flask equipped with a thermowell/K-thermocouple, stopper, nitrogen oil bubbler and magnetic stir bar. The stirred solution was cooled to about −5° C. with an acetone/ice bath. To this solution was added 55.96 grams of an aqueous 6.0 wt % calcium hypochlorite solution (3.36 grams of calcium hypochlorite, 23.5 mmoles, 65% available chlorine) dropwise over 44 minutes. Some undissolved solids were present in the calcium hypochlorite solution and were added as well. The temperature was kept below 0° C. during the addition. The pale yellow reaction mixture was allowed to stir at about 0° C. for 65 minutes. To the yellow reaction mixture was added 0.53 g (2.8 mmoles) of sodium metabisulfite, in portions as a solid to destroy any remaining oxidant. A white flocculant was present in the reaction mixture. It was removed by vacuum filtration of the entire reaction mixture through a medium sintered glass filter funnel. The filtrate was transferred to a separatory funnel and the phases were allowed to settle. The phases were separated and the aqueous phase re-extracted with acetonitrile (10 mL) and (15 mL). Sodium chloride (10.01 grams) was added to the aqueous phase during the second extraction to facilitate a phase break. The organics were combined and this acetonitrile/sulfilimine solution was used directly in the following oxidation. LC analysis indicated a 1.00:1.08 area ratio of the two sulfilimine isomers and showed sulfilimine at 80 area % and sulfoxide (two isomers) at 13 area %. equipped with a thermowell/K-thermocouple, stopper, nitrogen oil bubbler and magnetic stir bar were added as well The temperature was kept below 0° C. during the addition in portions as a solid to destroy any remaining oxidant It was removed by vacuum filtration of the entire reaction mixture through a medium sintered glass filter funnel The filtrate was transferred to a separatory funnel The phases were separated the aqueous phase re-extracted with acetonitrile (10 mL) and (15 mL) Sodium chloride (10.01 grams) was added to the aqueous phase during the second extraction

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

Procedure: 2.75 g (0.01 mol) of 2-(2,2,2-trifluoroethoxy)-5-(2,2,2-trifluoro-1-hydroxyethyl)pyridine and 0.18 g (0.0005 mol) of tetrabutylammonium hydrogen sulfate are dissolved in 20 ml of methylene chloride at room temperature. After addition of 4 ml of water and 1.72 g (0.012 mol) of calcium hypochlorite the mixture is stirred for 4 hours with vigorous mixing, during which the reaction temperature rises to 25 ° C. The reaction mixture is added to 50 ml of water, the phases are separated, the aqueous phase is extracted several times with methylene chloride and the combined organic phases are washed with saturated aqueous sodium chloride solution. After drying the organic phase with sodium sulfate, the volatiles are distilled off. Following distillation of the crude product in a kugelrohr (0.3 mbar, 100°-120° C. bath temperature), 2.38 g (87% of theory) of 2-(2,2,2-trifluoroethoxy)-5-trifluoroacetylpyridine are obtained. rises to 25 ° C the phases are separated the aqueous phase is extracted several times with methylene chloride the combined organic phases are washed with saturated aqueous sodium chloride solution After drying the organic phase with sodium sulfate the volatiles are distilled off distillation of the crude product in a kugelrohr (0.3 mbar, 100°-120° C. bath temperature), 2.38 g (87% of theory) of 2-(2,2,2-trifluoroethoxy)-5-trifluoroacetylpyridine are obtained

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

Procedure: 2.75 g (0.01 mol) of 2-(2,2,2-trifluoroethoxy)-5-(2,2,2-trifluoro-1-hydroxyethyl)pyridine and 0.18 g (0.0005 mol) of tetrabutylammonium hydrogen sulfate are dissolved in 20 ml of methylene chloride at room temperature. After addition of 4 ml of water and 1.72 g (0.012 mol) of calcium hypochlorite the mixture is stirred for 4 hours with vigorous mixing, during which the reaction temperature rises to 25 ° C. The reaction mixture is added to 50 ml of water, the phases are separated, the aqueous phase is extracted several times with methylene chloride and the combined organic phases are washed with saturated aqueous sodium chloride solution. After drying the organic phase with sodium sulfate, the volatiles are distilled off. Following distillation of the crude product in a kugelrohr (0.3 mbar, 100°-120° C. bath temperature), 2.38 g (87% of theory) of 2-(2,2,2-trifluoroethoxy)-5-trifluoroacetylpyridine are obtained. rises to 25 ° C the phases are separated the aqueous phase is extracted several times with methylene chloride the combined organic phases are washed with saturated aqueous sodium chloride solution After drying the organic phase with sodium sulfate the volatiles are distilled off distillation of the crude product in a kugelrohr (0.3 mbar, 100°-120° C. bath temperature), 2.38 g (87% of theory) of 2-(2,2,2-trifluoroethoxy)-5-trifluoroacetylpyridine are obtained