Reaction #420161

Reaction equation

tert-butyl 2-(hydroxymethyl)piperidine-1-carboxylate

NaH

2,6-dinitrobenzonitrile

→

tert-butyl 2-((2-cyano-3-nitrophenoxy)methyl)piperidine-1-carboxylate

Yield 70.6%

Solvents

water

THF

THF

DMF

Conditions

Workup

1. 1
   Other20 min
2. 2
   Otherat room temperature
3. 3
   Extractionextracted with EtOAc
4. 4
   Washthe combined organic phases were washed with brine
5. 5
   Dryingdried over MgSO4
6. 6
   Filtrationfiltered
7. 7
   Otherevaporated
8. 8
   OtherThe residue was purified by Biotage purification system (120 g Silicycle column, Hexane:EtOAc=3:2 as eluent)

Procedure

To a solution of tert-butyl 2-(hydroxymethyl)piperidine-1-carboxylate (0.86 g, 4 mmol) in dry THF (30 mL) was added at −20° C. NaH (0.32 g, 8 mmol) and the mixture was stirred 10 min at −20° C. and then 20 min at room temperature. The reaction mixture was then cooled to −20° C. and 2,6-dinitrobenzonitrile (0.772 g, 4 mmol) in dry THF (10 mL) and DMF (1 mL) was added dropwise over 15 min period. The solution was stirred under nitrogen at room temperature for 18 hours, diluted with water and extracted with EtOAc, the combined organic phases were washed with brine, dried over MgSO4, filtered and evaporated. The residue was purified by Biotage purification system (120 g Silicycle column, Hexane:EtOAc=3:2 as eluent) to give tert-butyl 2-((2-cyano-3-nitrophenoxy)methyl)piperidine-1-carboxylate (1.02 g, 70.6%). MS 262 [M+H-Boc]+.

Source