Reaction #1121808

Reaction equation

iodomethane

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

sodium hydride

Water

→

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

Yield 79.0%

Solvents

DMF

DMF

Conditions

Workup

1. 1
   workup.STIRRINGto stir at room temperature for 2 hours
2. 2
   TemperatureThen the mixture was cooled to 0° C.
3. 3
   workup.STIRRINGThe reaction mixture was stirred at 0° C. for 1 hour
4. 4
   Temperatureto warm to room temperature over 18 hours
5. 5
   Extractionthe mixture was extracted into EtOAc (3×50 mL)
6. 6
   Washwashed with water (3×20 mL)
7. 7
   Dryingdried (MgSO4)
8. 8
   Filtrationfiltered
9. 9
   Concentrationconcentrated in vacuo
10. 10
    OtherThe residue obtained
11. 11
    Otherwas purified by flash chromatography on silica gel (Biotage Flash 40M+)
12. 12
    Washeluting with 20% EtOAc/hexane (1.25 L)

Procedure

A solution of (R)-benzyl 3-(tert-butoxycarbonylamino)piperidine-1-carboxylate (5.00 g, 14.95 mmol) 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. Then the mixture was cooled to 0° C. and treated dropwise with iodomethane (1.024 mL, 16.45 mmol). The reaction mixture was stirred at 0° C. for 1 hour and allowed to warm to room temperature over 18 hours. Water (40 mL) was added, and the mixture was extracted into EtOAc (3×50 mL). The organic layers were combined, washed with water (3×20 mL), dried (MgSO4), filtered, and concentrated in vacuo. The residue obtained was purified by flash chromatography on silica gel (Biotage Flash 40M+) eluting with 20% EtOAc/hexane (1.25 L) to provide (R)-benzyl 3-(tert-butoxycarbonyl(methyl)amino)piperidine-1-carboxylate (4.10 g, 79% yield) as an oil. LCMS (APCI+) m/z 349 (M+H)+.

Source