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 and 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 for 30 min at RT, cooled to 0° C., and treated dropwise with 1,2-dibromoethane (5.17 mL, 58.8 mmol). The mixture was allowed to warm to room temperature while stirring overnight. The mixture was quenched with saturated ammonium chloride (100 mL) and then extracted with diethyl ether (4×50 mL). The combined organic layers were washed with 50% saturated sodium chloride (4×50 mL), dried (MgSO4), filtered and the filtrate concentrated in vacuo. The 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 1.33 (t, J=7.05 Hz, 3H) 1.64 (s, 3H) 2.49-2.59 (m, 1H) 2.78 (ddd, J=13.89, 10.16, 6.64 Hz, 1H) 3.05 (s, 3H) 3.33-3.41 (m, 1H) 3.46-3.54 (m, 1H) 4.22-4.37 (m, 2H).

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. extractionextracted with diethyl ether (4×50 mL)
6. washThe combined organic layers were washed with 50% saturated sodium chloride (4×50 mL)
7. dry with materialdried (MgSO4)
8. filtrationfiltered
9. concentrationthe filtrate concentrated in vacuo
10. customThe crude material was chromatographed over silica gel (350 g, 230-400 mesh)
11. washeluting with 10-20% EtOAc/hexane

ORD record

ord-b29c95dbab6541128947ff15b347cb21

Source dataset

uspto-grants-2014_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08809333B2