tert-butyl N-(oxan-4-ylideneamino)carbamate

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

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

Procedure: N′-(Tetrahydro-pyran-4-ylidene)-hydrazinecarboxylic acid tert-butyl ester (5.210 g, 24.32 mmol) was dissolved in a mixture of dry tetrahydrofuran (22 mL) and dry methanol (30 mL). Sodium cyanoborohydride was added to the solution resulting in effervescence. When the effervescence subsided, the mixture was heated to reflux for 5-10 minutes. After cooling to room temperature 6N HCl (10.5 mL) was slowly added and then the mixture was heated to reflux for 20 minutes. After cooling to room temperature, the solvent was removed in vacuo. The residue was triturated with hot isopropanol and then cooled to room temperature, diluted with ether and chilled. The solid was collected by filtration and was found to be the reduced material but not completely deprotected. The solid was dissolved in the same THF-methanol mixture and treated with 6N HCl (10.5 mL) at reflux for another 1.5 hours. After cooling to room temperature, the reaction mixture was filtered to remove a small amount of insoluble material. The filtrate was then concentrated in vacuo. Isopropanol was added to the residue and solid quickly began to crystallize out of solution. After chilling overnight, ether was added followed by additional chilling. The solid was then collected by filtration, washed with ether and dried in vacuo to give (tetrahydro-pyran-4-yl)-hydrazine hydrochloride (2.22 g, 60%). resulting in effervescence the mixture was heated to reflux for 5-10 minutes was slowly added the mixture was heated to reflux for 20 minutes the solvent was removed in vacuo The residue was triturated with hot isopropanol cooled to room temperature diluted with ether chilled The solid was collected by filtration The solid was dissolved in the same THF-methanol mixture treated with 6N HCl (10.5 mL) at reflux for another 1.5 hours After cooling to room temperature the reaction mixture was filtered to remove a small amount of insoluble material The filtrate was then concentrated in vacuo Isopropanol was added to the residue and solid to crystallize out of solution After chilling overnight ether was added The solid was then collected by filtration washed with ether dried in vacuo

Conditions: temp:67.51; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Tetrahydro-4H-pyran-4-one (1.002 g, 10.01 mmol, CAS #29943-42-8, purchased from Fluka) was combined with tert-butyl carbazate (1.322 g, 10.00 mmol) in hexanes (10 mL). The mixture was heated in an oil bath at 65-70° C. for 75 minutes. A new precipitate began to precipitate out of solution before the carbazate completely went into solution. The mixture became very thick with the solid precipitate. Diluted with additional hexanes and heated another 15 minutes. The mixture was cooled to room temperature and concentrated in vacuo. Isopropanol was added to the residue and the mixture was stirred vigorously for 5 minutes and then diluted with ether and chilled. The solid was collected by filtration and dried in vacuo to give N′-(tetrahydro-pyran-4-ylidene)-hydrazinecarboxylic acid tert-butyl ester 1.326 g, 62%). A second crop (0.373 g, 17%) was collected from the mother liquor. to precipitate out of solution before the carbazate Diluted with additional hexanes heated another 15 minutes The mixture was cooled to room temperature concentrated in vacuo Isopropanol was added to the residue diluted with ether chilled The solid was collected by filtration dried in vacuo

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

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

Procedure: N′-(Tetrahydro-pyran-4-ylidene)-hydrazinecarboxylic acid tert-butyl ester (5.210 g, 24.32 mmol) was dissolved in a mixture of dry tetrahydrofuran (22 mL) and dry methanol (30 mL). Sodium cyanoborohydride was added to the solution resulting in effervescence. When the effervescence subsided, the mixture was heated to reflux for 5-10 minutes. After cooling to room temperature 6N HCl (10.5 mL) was slowly added and then the mixture was heated to reflux for 20 minutes. After cooling to room temperature, the solvent was removed in vacuo. The residue was triturated with hot isopropanol and then cooled to room temperature, diluted with ether and chilled. The solid was collected by filtration and was found to be the reduced material but not completely deprotected. The solid was dissolved in the same THF-methanol mixture and treated with 6N HCl (10.5 mL) at reflux for another 1.5 hours. After cooling to room temperature, the reaction mixture was filtered to remove a small amount of insoluble material. The filtrate was then concentrated in vacuo. Isopropanol was added to the residue and solid quickly began to crystallize out of solution. After chilling overnight, ether was added followed by additional chilling. The solid was then collected by filtration, washed with ether and dried in vacuo to give (tetrahydro-pyran-4-yl)-hydrazine hydrochloride (2.22 g, 60%). resulting in effervescence the mixture was heated to reflux for 5-10 minutes was slowly added the mixture was heated to reflux for 20 minutes the solvent was removed in vacuo The residue was triturated with hot isopropanol cooled to room temperature diluted with ether chilled The solid was collected by filtration The solid was dissolved in the same THF-methanol mixture treated with 6N HCl (10.5 mL) at reflux for another 1.5 hours After cooling to room temperature the reaction mixture was filtered to remove a small amount of insoluble material The filtrate was then concentrated in vacuo Isopropanol was added to the residue and solid to crystallize out of solution After chilling overnight ether was added The solid was then collected by filtration washed with ether dried in vacuo

Conditions: temp:67.51; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Tetrahydro-4H-pyran-4-one (1.002 g, 10.01 mmol, CAS #29943-42-8, purchased from Fluka) was combined with tert-butyl carbazate (1.322 g, 10.00 mmol) in hexanes (10 mL). The mixture was heated in an oil bath at 65-70° C. for 75 minutes. A new precipitate began to precipitate out of solution before the carbazate completely went into solution. The mixture became very thick with the solid precipitate. Diluted with additional hexanes and heated another 15 minutes. The mixture was cooled to room temperature and concentrated in vacuo. Isopropanol was added to the residue and the mixture was stirred vigorously for 5 minutes and then diluted with ether and chilled. The solid was collected by filtration and dried in vacuo to give N′-(tetrahydro-pyran-4-ylidene)-hydrazinecarboxylic acid tert-butyl ester 1.326 g, 62%). A second crop (0.373 g, 17%) was collected from the mother liquor. to precipitate out of solution before the carbazate Diluted with additional hexanes heated another 15 minutes The mixture was cooled to room temperature concentrated in vacuo Isopropanol was added to the residue diluted with ether chilled The solid was collected by filtration dried in vacuo

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

Procedure: B-22a was prepared analogously to B-19a starting from tetrahydro-4H-pyran-4-one (923 μL, 9.99 mmol) and tert-butylcarbazate (1.32 g, 9.99 mmol). Yield: 2.15 g. B-22a was prepared analogously to B-19a

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

Procedure: N′-(Tetrahydro-pyran-4-ylidene)-hydrazinecarboxylic acid tert-butyl ester (5.210 g, 24.32 mmol) was dissolved in a mixture of dry tetrahydrofuran (22 mL) and dry methanol (30 mL). Sodium cyanoborohydride was added to the solution resulting in effervescence. When the effervescence subsided, the mixture was heated to reflux for 5-10 minutes. After cooling to room temperature 6N HCl (10.5 mL) was slowly added and then the mixture was heated to reflux for 20 minutes. After cooling to room temperature, the solvent was removed in vacuo. The residue was triturated with hot isopropanol and then cooled to room temperature, diluted with ether and chilled. The solid was collected by filtration and was found to be the reduced material but not completely deprotected. The solid was dissolved in the same THF-methanol mixture and treated with 6N HCl (10.5 mL) at reflux for another 1.5 hours. After cooling to room temperature, the reaction mixture was filtered to remove a small amount of insoluble material. The filtrate was then concentrated in vacuo. Isopropanol was added to the residue and solid quickly began to crystallize out of solution. After chilling overnight, ether was added followed by additional chilling. The solid was then collected by filtration, washed with ether and dried in vacuo to give (tetrahydro-pyran-4-yl)-hydrazine hydrochloride (2.22 g, 60%). resulting in effervescence the mixture was heated to reflux for 5-10 minutes was slowly added the mixture was heated to reflux for 20 minutes the solvent was removed in vacuo The residue was triturated with hot isopropanol cooled to room temperature diluted with ether chilled The solid was collected by filtration The solid was dissolved in the same THF-methanol mixture treated with 6N HCl (10.5 mL) at reflux for another 1.5 hours After cooling to room temperature the reaction mixture was filtered to remove a small amount of insoluble material The filtrate was then concentrated in vacuo Isopropanol was added to the residue and solid to crystallize out of solution After chilling overnight ether was added The solid was then collected by filtration washed with ether dried in vacuo

Conditions: temp:67.51; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Tetrahydro-4H-pyran-4-one (1.002 g, 10.01 mmol, CAS #29943-42-8, purchased from Fluka) was combined with tert-butyl carbazate (1.322 g, 10.00 mmol) in hexanes (10 mL). The mixture was heated in an oil bath at 65-70° C. for 75 minutes. A new precipitate began to precipitate out of solution before the carbazate completely went into solution. The mixture became very thick with the solid precipitate. Diluted with additional hexanes and heated another 15 minutes. The mixture was cooled to room temperature and concentrated in vacuo. Isopropanol was added to the residue and the mixture was stirred vigorously for 5 minutes and then diluted with ether and chilled. The solid was collected by filtration and dried in vacuo to give N′-(tetrahydro-pyran-4-ylidene)-hydrazinecarboxylic acid tert-butyl ester 1.326 g, 62%). A second crop (0.373 g, 17%) was collected from the mother liquor. to precipitate out of solution before the carbazate Diluted with additional hexanes heated another 15 minutes The mixture was cooled to room temperature concentrated in vacuo Isopropanol was added to the residue diluted with ether chilled The solid was collected by filtration dried in vacuo