(dibutylamino) thiohypochlorite

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

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

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

Procedure: To a stirred mixture of N-[4-(4-methylthiophenoxy)benzyl]-4-chloro-1,3-dimethylpyrazole-5-carboxamide (300 mg, 0.746 mM), 4-(N,N-dimethylamino)pyridine (119 mg, 0.970 mM) and dry pyridine (5 ml) was added dropwise N,N-di-n-butylaminosulfenyl chloride (190 mg, 0.970 mM) at 0°-10° C., and the mixture was stirred for 4 h at the room temperature. The mixture was poured into ice water, and the mixture was extracted with dichloromethane. The extract was washed with saturated ammonium chloride solution(x2) and brine, dried with sodium sulfate, and concentrated in vacuo. The residue was chromatographed over silica gel to give N-(N,N-di-n-butylaminosulfenyl)-N-[4-(4-methylthiophenoxy)benzyl]4-chloro-1,3-dimethylpyrazole-5-carboxamide (217 mg, 52%) as a colorless oil, nD23.3 1.5748. the mixture was extracted with dichloromethane The extract was washed with saturated ammonium chloride solution(x2) and brine dried with sodium sulfate concentrated in vacuo The residue was chromatographed over silica gel

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

Procedure: To a stirred mixture of N-[4-(4-methylthiophenoxy)benzyl]-4-chloro-1,3-dimethylpyrazole-5-carboxamide (300 mg, 0.746 mM), 4-(N,N-dimethylamino)pyridine (119 mg, 0.970 mM) and dry pyridine (5 ml) was added dropwise N,N-di-n-butylaminosulfenyl chloride (190 mg, 0.970 mM) at 0°-10° C., and the mixture was stirred for 4 h at the room temperature. The mixture was poured into ice water, and the mixture was extracted with dichloromethane. The extract was washed with saturated ammonium chloride solution(x2) and brine, dried with sodium sulfate, and concentrated in vacuo. The residue was chromatographed over silica gel to give N-(N,N-di-n-butylaminosulfenyl)-N-[4-(4-methylthiophenoxy)benzyl]4-chloro-1,3-dimethylpyrazole-5-carboxamide (217 mg, 52%) as a colorless oil, nD23.3 1.5748. the mixture was extracted with dichloromethane The extract was washed with saturated ammonium chloride solution(x2) and brine dried with sodium sulfate concentrated in vacuo The residue was chromatographed over silica gel

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

Procedure: To a solution of the title compound of Step B (Example 1) (0.4 g, 0.96 mmol) in 8 ml methylene chloride cooled to 0° C. was added triethylamine (0.15 g) and dibutylaminosulfenylchloride (0.2 g). The reaction mixture was, warmed to room temperature and stirred for one hour. The mixture was subjected to silica gel column chromatography using hexane-ether (6:1) as the eluent. The title compound was obtained (0.24 g) in high purity.

Conditions: temp:9.51; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Sulfur dioxide was passed through 30.2 g of a 50% solution of dibutylaminosulfenyl chloride (0.077 mole) in hexane until the solution had gained 2.8 g (0.044 mole). 2,3-Dihydro-2,2-dimethyl-7-benzofuranyl methylcarbamate (98%, 15.5 g, 0.069 mole) was added followed by dropwise addition of triethylamine (12.4 g, 0.123 mole) over a period of 28 minutes with stirring. Stirring was continued for about 18 hours. The mixture was cooled to 9.5° C., 31 ml of water and 40 ml of hexane were added, and the layers were separated. The organic layer was concentrated to yield 27.4 g of 94% (by hplc) 2,3-dihydro-2,2-dimethyl-7-benzofuranyl (dibutylaminothio)methylcarbamate (98% chemical yield). Stirring the layers were separated The organic layer was concentrated

Conditions: temp:9.51; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Sulfur dioxide was passed through 30.2 g of a 50% solution of dibutylaminosulfenyl chloride (0.077 mole) in hexane until the solution had gained 2.8 g (0.044 mole). 2,3-Dihydro-2,2-dimethyl-7-benzofuranyl methylcarbamate (98%, 15.5 g, 0.069 mole) was added followed by dropwise addition of triethylamine (12.4 g, 0.123 mole) over a period of 28 minutes with stirring. Stirring was continued for about 18 hours. The mixture was cooled to 9.5° C., 31 ml of water and 40 ml of hexane were added, and the layers were separated. The organic layer was concentrated to yield 27.4 g of 94% (by hplc) 2,3-dihydro-2,2-dimethyl-7-benzofuranyl (dibutylaminothio)methylcarbamate (98% chemical yield). Stirring the layers were separated The organic layer was concentrated

Conditions: temp:35.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A flask was charged with 15.8 g of 98% 2,3-dihydro-2,2-dimethyl-7-benzofuranyl methylcarbamate (0.07 mole) and 30.2 g of a 50% solution of dibutylaminosulfenyl chloride (0.077 mole) in hexane under nitrogen atmosphere. To this was added with stirring 7.5 g (0.0455 mole) of triethylamine/sulfur dioxide complex prepared as described in Example 3. Pyridine (6.1 g, 0.077 mole) was then added dropwise with stirring over a period of 16 minutes. The temperature increased from 20.5° C. to 23.5° C. Stirring was continued for three hours after the beginning of pyridine addition during which external heating was supplied to maintain a temperature of 35° C. The mixture was cooled to 10.5° C. and 31 ml of water was added. The mixture was filtered, separated, and the organic layer was concentrated to yield 18.99 g of 75% (by hplc) 2,3-dihydro-2,2-dimethyl-7-benzofuranyl (dibutylaminothio)methylcarbamate (53% chemical yield based on the starting carbamate). To this was added prepared with stirring over a period of 16 minutes The temperature increased from 20.5° C. to 23.5° C Stirring external heating The mixture was cooled to 10.5° C. The mixture was filtered separated the organic layer was concentrated

Conditions: temp:11.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A flask was charged with 30.2 g of a 50% solution of dibutylaminosulfenyl chloride (0.077 mole) in hexane and 15.8 g of 98% 2,3-dihydro-2,2-dimethyl-7-benzofuranyl methylcarbamate (0.07 mole) was added. Triethylamine (7.8 g, 0.077 mole) was added to the mixture with agitation over a period of seven minutes. A temperature rise from 24.5° to 26° C. was observed. A portion (1.9 g, 0.0115 mole) of the triethylamine/sulfur dioxide catalyst prepared in Example 3 was added dropwise. The temperature gradually rose to 30° C., and was raised further by external heating to 35° C. for a total reaction time of 100 minutes from the beginning of triethylamine addition. Twenty minutes later the mixture was cooled to 11° C. and 31 ml of water was added and mixed. The mixture was filtered to remove a small amount of solid, separated, and the organic layer was concentrated to yield 26.64 g of 90% (hplc) 2,3-dihydro-2,2-dimethyl-7-benzofuranyl (dibutylaminothio)methylcarbamate (a 90% chemical yield based on the starting carbamate). was added from 24.5° to 26° C. gradually rose to 30° C. was raised further mixed The mixture was filtered to remove a small amount of solid separated the organic layer was concentrated

Conditions: temp:11.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A flask was charged with 30.2 g of a 50% solution of dibutylaminosulfenyl chloride (0.077 mole) in hexane and 15.8 g of 98% 2,3-dihydro-2,2-dimethyl-7-benzofuranyl methylcarbamate (0.07 mole) was added. Triethylamine (7.8 g, 0.077 mole) was added to the mixture with agitation over a period of seven minutes. A temperature rise from 24.5° to 26° C. was observed. A portion (1.9 g, 0.0115 mole) of the triethylamine/sulfur dioxide catalyst prepared in Example 3 was added dropwise. The temperature gradually rose to 30° C., and was raised further by external heating to 35° C. for a total reaction time of 100 minutes from the beginning of triethylamine addition. Twenty minutes later the mixture was cooled to 11° C. and 31 ml of water was added and mixed. The mixture was filtered to remove a small amount of solid, separated, and the organic layer was concentrated to yield 26.64 g of 90% (hplc) 2,3-dihydro-2,2-dimethyl-7-benzofuranyl (dibutylaminothio)methylcarbamate (a 90% chemical yield based on the starting carbamate). was added from 24.5° to 26° C. gradually rose to 30° C. was raised further mixed The mixture was filtered to remove a small amount of solid separated the organic layer was concentrated

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

Procedure: To a stirred mixture of N-[4-(4-methylthiophenoxy)benzyl]-4-chloro-1,3-dimethylpyrazole-5-carboxamide (300 mg, 0.746 mM), 4-(N,N-dimethylamino)pyridine (119 mg, 0.970 mM) and dry pyridine (5 ml) was added dropwise N,N-di-n-butylaminosulfenyl chloride (190 mg, 0.970 mM) at 0°-10° C., and the mixture was stirred for 4 h at the room temperature. The mixture was poured into ice water, and the mixture was extracted with dichloromethane. The extract was washed with saturated ammonium chloride solution(x2) and brine, dried with sodium sulfate, and concentrated in vacuo. The residue was chromatographed over silica gel to give N-(N,N-di-n-butylaminosulfenyl)-N-[4-(4-methylthiophenoxy)benzyl]4-chloro-1,3-dimethylpyrazole-5-carboxamide (217 mg, 52%) as a colorless oil, nD23.3 1.5748. the mixture was extracted with dichloromethane The extract was washed with saturated ammonium chloride solution(x2) and brine dried with sodium sulfate concentrated in vacuo The residue was chromatographed over silica gel

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

Procedure: To a solution of the title compound of Step B (Example 1) (0.4 g, 0.96 mmol) in 8 ml methylene chloride cooled to 0° C. was added triethylamine (0.15 g) and dibutylaminosulfenylchloride (0.2 g). The reaction mixture was, warmed to room temperature and stirred for one hour. The mixture was subjected to silica gel column chromatography using hexane-ether (6:1) as the eluent. The title compound was obtained (0.24 g) in high purity.