Reaction #632007

Reaction equation

n-butyllithium

methyl iodide

N-tert-butyl-(3-chloro)propylsulfonamide

n-butyllithium

→

desired product

N-tert-butyl-(1-methyl)cyclopropyl-sulfonamide

Solvents

THF

Conditions

Workup

1. 1
   OtherThe dry ice bath was removed
2. 2
   Temperaturethe reaction mixture was warmed to room temperature over a period of 1.5 hours
3. 3
   TemperatureThis mixture was cooled to −78° C.
4. 4
   TemperatureThe reaction mixture was warmed to room temperature
5. 5
   Temperaturecooled to −78° C. over a period of 2 hours
6. 6
   TemperatureThe reaction mixture was warmed to room temperature overnight
7. 7
   Otherquenched with saturated NH4Cl (100 mL) at room temperature
8. 8
   Extractionextracted with ethyl acetate (100 mL)
9. 9
   WashThe organic phase was washed with brine (100 mL)
10. 10
    Dryingdried (MgSO4)
11. 11
    Filtrationfiltered
12. 12
    Concentrationconcentrated in vacuo
13. 13
    Otherto provide a yellow oil which
14. 14
    Otherwas crystallized from hexane

Procedure

A solution of N-tert-butyl-(3-chloro)propylsulfonamide (4.3 g, 20 mmol) was dissolved in dry THF (100 mL) and cooled to −78° C. To this solution was added n-butyllithium (17.6 mL, 44 mmol, 2.5M in hexane) slowly. The dry ice bath was removed and the reaction mixture was warmed to room temperature over a period of 1.5 hours. This mixture was cooled to −78° C. and a solution of n-butyllithium (20 mmol, 8 mL, 2.5M in hexane) was added. The reaction mixture was warmed to room temperature, cooled to −78° C. over a period of 2 hours, and treated with a neat solution of methyl iodide (5.68 g, 40 mmol). The reaction mixture was warmed to room temperature overnight, then quenched with saturated NH4Cl (100 mL) at room temperature and extracted with ethyl acetate (100 mL). The organic phase was washed with brine (100 mL), dried (MgSO4), filtered, and concentrated in vacuo to provide a yellow oil which was crystallized from hexane to provide the desired product as a slightly yellow solid (3.1 g, 81%): 1H NMR (CDCl3) δ 0.79 (m, 2H), 1.36 (s, 9H), 1.52 (m, 2H), 1.62 (s, 3H), 4.10 (br s, 1H).

Source