Bromoacetonitrile → HCID 18702190, compound

Temperature

-15 °C

To a 300 mL reaction flask was added 2.4 g (59.3 mmole) sodium hydride (60% dispersion in oil) and 10 mL hexanes. The hexanes were removed by pipette and replaced by 60 mL dry tetrahydrofuran (THF). The suspension was cooled to -15° C. and a solution of 12.0 g (51.6 mmole) 4-chlorophenylsulfonyl acetone in 50 mL THF was added via addition funnel over 20 minutes maintaining the reaction temperature below -12° C. The resulting yellow solution was removed from the cold bath and stirred at room temperature for 30 min. The solution was recooled to -5° C. and 3.8 mL (54.1 mmole) bromoacetonitrile was added dropwise via addition funnel. After 5 min, the reaction mixture was removed from the cold bath and stirred at room temperature overnight. The reaction was quenched with 1 mL of saturated ammonium chloride and transferred with 100 mL of dichloromethane to a separatory funnel containing 100 mL brine. The organic layer was separated and the aqueous layer was back extracted once with 50 mL more dichloromethane. The combined organics were then dried with sodium sulfate, filtered, concentrated, and chromatographed through a bed of silica gel using 1:1 hexane:dichloromethane. Isolation gave 8.2 g (59% yield) of 3-(4-chlorophenylsulfonyl)4-cyanobutan-2-one, a yellow oil that was 90% pure by HPLC. 1H NMR (CDCl3) indicated desired product as the major component: δ7.6 (m, 4H), 4.42 (dd, 1H), 2.78 (m, 2H), 2.48 (s, 3H).

1. customTo a 300 mL reaction flask
2. customThe hexanes were removed by pipette
3. temperaturemaintaining the reaction temperature below -12° C
4. customThe resulting yellow solution was removed from the cold bath
5. customwas recooled to -5° C.
6. waitAfter 5 min
7. customthe reaction mixture was removed from the cold bath
8. stirringstirred at room temperature overnight
9. customThe reaction was quenched with 1 mL of saturated ammonium chloride
10. customtransferred with 100 mL of dichloromethane to a separatory funnel
11. additioncontaining 100 mL brine
12. customThe organic layer was separated
13. extractionthe aqueous layer was back extracted once with 50 mL more dichloromethane
14. dry with materialThe combined organics were then dried with sodium sulfate
15. filtrationfiltered
16. concentrationconcentrated
17. customchromatographed through a bed of silica gel using 1:1 hexane

ORD record

ord-b8eee44cb9c14e44ac41c4925f5732a1

Source dataset

uspto-grants-2000_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06090927