1,2-Dibromoethane → Ethyl 4-bromo-2-methyl-2-(methylsulfonyl)butanoate

Sodium hydride (60% dispersion in mineral oil, 2.33 g, 58.3 mmol) was washed with hexane (2×10 mL) in a 100 mL two neck round bottom flask under nitrogen then suspended in DMF (30 mL). The suspension was treated dropwise with ethyl 2-(methylsulfonyl)propanoate (10.0 g, 55.49 mmol) in DMF (10 mL). The mixture was stirred 30 min at RT, cooled to 0° C., and treated dropwise with 1,2-dibromoethane (5.17 mL, 58.8). The mixture was allowed to warm to room temperature while stirring overnight. The mixture was quenched with saturated ammonium chloride (100 mL) and the mixture was extracted with diethyl ether (4×50 mL). Combined organics were washed with 50% saturated sodium chloride (4×50 mL), dried (MgSO4), filtered and the filtrate concentrated in vacuo. Crude material was chromatographed over silica gel (350 g, 230-400 mesh) eluting with 10-20% EtOAc/hexane to afford the title compound as a pale yellow oil (7.9 g, 50%). 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 1.33 (t, J=7.05 Hz, 3 H) 1.64 (s, 3 H) 2.49-2.59 (m, 1 H) 2.78 (ddd, J=13.89, 10.16, 6.64 Hz, 1 H) 3.05 (s, 3 H) 3.33-3.41 (m, 1 H) 3.46-3.54 (m, 1 H) 4.22-4.37 (m, 2 H).

1. temperaturecooled to 0° C.
2. temperatureto warm to room temperature
3. stirringwhile stirring overnight
4. customThe mixture was quenched with saturated ammonium chloride (100 mL)
5. extractionthe mixture was extracted with diethyl ether (4×50 mL)
6. washCombined organics were washed with 50% saturated sodium chloride (4×50 mL)
7. dry with materialdried (MgSO4)
8. filtrationfiltered
9. concentrationthe filtrate concentrated in vacuo
10. customCrude material was chromatographed over silica gel (350 g, 230-400 mesh)
11. washeluting with 10-20% EtOAc/hexane

ORD record

ord-f65a0b8f9b59409eb0587c248183b47e

Source dataset

uspto-grants-2014_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08846933B2