Reaction #1121809

Reaction equation

iodoethane

(R)-benzyl 3-(tert-butoxycarbonylamino)piperidine-1-carboxylate

sodium hydride

Water

→

(R)-benzyl 3-(tert-butoxycarbonyl(ethyl)amino)piperidine-1-carboxylate

Yield 92.5%

Solvents

DMF

DMF

Conditions

Workup

1. 1
   workup.STIRRINGto stir at room temperature for 2 hours
2. 2
   TemperatureThe mixture was then cooled to 0° C.
3. 3
   workup.STIRRINGThe reaction mixture was stirred at 0° C. for 2 hours
4. 4
   Temperatureto warm to room temperature over 18 hours
5. 5
   Extractionthe mixture was extracted into EtOAc (3×70 mL)
6. 6
   Washwashed with water (3×20 mL)
7. 7
   Dryingdried (MgSO4)
8. 8
   Filtrationfiltered
9. 9
   Concentrationconcentrated in vacuo
10. 10
    OtherThe resulting residue was purified by flash chromatography on silica gel (Biotage Flash 40M+)
11. 11
    Washeluting with 20% EtOAc/hexane

Procedure

A solution of (R)-benzyl 3-(tert-butoxycarbonylamino)piperidine-1-carboxylate (5.00 g, 14.95 mmol, Example E) in dry DMF (50 mL) was added dropwise to a suspension of sodium hydride 60% in mineral oil (0.7176 g, 17.94 mmol) in dry DMF (10 mL). The mixture was stirred at 0° C. for 1 hour and allowed to stir at room temperature for 2 hours. The mixture was then cooled to 0° C. and treated dropwise with iodoethane (1.315 mL, 16.45 mmol). The reaction mixture was stirred at 0° C. for 2 hours and allowed to warm to room temperature over 18 hours. Water (50 mL) was added, and the mixture was extracted into EtOAc (3×70 mL). The organic layers were combined, washed with water (3×20 mL), dried (MgSO4), filtered, and concentrated in vacuo. The resulting residue was purified by flash chromatography on silica gel (Biotage Flash 40M+) eluting with 20% EtOAc/hexane to provide (R)-benzyl 3-(tert-butoxycarbonyl(ethyl)amino)piperidine-1-carboxylate (5.01 g, 92% yield) as an oil. LCMS (APCI+) m/z 363 (M+H)+.

Source