Reaction #41160

Reaction equation

N′-(Tetrahydro-pyran-4-ylidene)-hydrazinecarboxylic acid tert-butyl ester

Sodium cyanoborohydride

HCl

→

(tetrahydro-pyran-4-yl)-hydrazine hydrochloride

Yield 60.0%

Solvents

tetrahydrofuran

methanol

Conditions

Workup

1. 1
   Otherresulting in effervescence
2. 2
   Temperaturethe mixture was heated
3. 3
   Temperatureto reflux for 5-10 minutes
4. 4
   workup.ADDITIONwas slowly added
5. 5
   Temperaturethe mixture was heated
6. 6
   Temperatureto reflux for 20 minutes
7. 7
   Otherthe solvent was removed in vacuo
8. 8
   OtherThe residue was triturated with hot isopropanol
9. 9
   Temperaturecooled to room temperature
10. 10
    workup.ADDITIONdiluted with ether
11. 11
    Temperaturechilled
12. 12
    FiltrationThe solid was collected by filtration
13. 13
    workup.DISSOLUTIONThe solid was dissolved in the same THF-methanol mixture
14. 14
    workup.ADDITIONtreated with 6N HCl (10.5 mL)
15. 15
    Temperatureat reflux for another 1.5 hours
16. 16
    TemperatureAfter cooling to room temperature
17. 17
    Filtrationthe reaction mixture was filtered
18. 18
    Otherto remove a small amount of insoluble material
19. 19
    ConcentrationThe filtrate was then concentrated in vacuo
20. 20
    workup.ADDITIONIsopropanol was added to the residue and solid
21. 21
    Otherto crystallize out of solution
22. 22
    TemperatureAfter chilling overnight
23. 23
    workup.ADDITIONether was added
24. 24
    FiltrationThe solid was then collected by filtration
25. 25
    Washwashed with ether
26. 26
    Otherdried in vacuo

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%).

Source