Reaction #674301

Reaction equation

Methanesulfonyl chloride

NH4Cl

Et3N

Et3N

methanesulfonyl chloride

tert-butyl 2-hydroxy-7-azaspiro[3.5]nonane-7-carboxylate

→

tert-butyl 2-(methylsulfonyloxy)-7-azaspiro[3.5]nonane-7-carboxylate

Yield 93.1%

Solvents

DCM

Conditions

Workup

1. 1
   Temperatureto warm to room temperature
2. 2
   workup.STIRRINGstirred at room temperature for 18 hrs
3. 3
   workup.STIRRINGthe mixture was stirred for another 6 h
4. 4
   workup.STIRRINGstirred at room temperature for 10 min
5. 5
   OtherThe layers were separated
6. 6
   ExtractionThe aqueous phase was extracted with DCM (3×30 mL)
7. 7
   WashThe combined organic phase were washed with HCl (1N, 20 mL) and water (20 mL)
8. 8
   Dryingwere dried over anhydrous Na2SO4
9. 9
   Concentrationconcentrated in vacuo

Procedure

tert-butyl 2-hydroxy-7-azaspiro[3.5]nonane-7-carboxylate (392 mg, 1.62 mmol, 1.0 equiv) was dissolved in DCM (6.0 mL). The solution was cooled to 0° C. with an external ice-bath. Et3N (237 μL, 1.706 mmol, 1.05 equiv)) and DMAP (2.0 mg, 1 mol %) were added. Methanesulfonyl chloride (132 μL, 1.706 mmol, 1.05 equiv) was then added dropwise by a syringe. The solution was stirred at 0° C. for 2.0 hrs, was then allowed to warm to room temperature and stirred at room temperature for 18 hrs. Et3N (23 μL, 0.1 equiv) and methanesulfonyl chloride (13 μL, 0.1 equiv) were added and the mixture was stirred for another 6 h. A saturated solution of NH4Cl (20 mL) was added and stirred at room temperature for 10 min. The layers were separated. The aqueous phase was extracted with DCM (3×30 mL). The combined organic phase were washed with HCl (1N, 20 mL) and water (20 mL) and were dried over anhydrous Na2SO4, concentrated in vacuo to afford 482 mg (yield 93%) of tert-butyl 2-(methylsulfonyloxy)-7-azaspiro[3.5]nonane-7-carboxylate as a white solid.

Source