Uses
5,5-Dimethyl-2-pyrrolidone, is a versatile building block used in the synthesis of various chemical compounds, such as novel, Induced-pocket binding oxazolidinones as potent, selective, and orally bioavailable tankyrase inhibitors.
Synthesis
General procedure for the synthesis of 5,5-dimethyl-2-pyrrolidinone from methyl 4-methyl-4-nitrovalerate: synthesis of compound 218.2. Sodium borohydride (0.717 g, 11.428 mmol, 2.0 eq.) was slowly added to a methanol (10 mL) solution of nickel chloride (2.291 g, 11.428 mmol, 2.0 eq.), and the reaction mixture was stirred for 30 min at room temperature. Subsequently, methyl 4-methyl-4-nitrovalerate (1.0 g, 5.714 mmol, 1.0 eq.) was added dropwise to the above reaction mixture and stirring was continued at room temperature for 16 hours. After completion of the reaction, the solvent was removed by distillation under reduced pressure and water was added to the residue. The aqueous phase was extracted with ethyl acetate, the organic layers were combined, dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure to give the crude product. The crude product was purified by fast column chromatography to afford the target compound 218.2 (0.250 g, 38.70% yield), mass spectrum (electrospray ionization): m/z 113.16 [M + H]+.
References
[1] Chemical Communications, 2012, vol. 48, # 84, p. 10440 - 10442
[2] Tetrahedron Letters, 1985, vol. 26, # 52, p. 6413 - 6416
[3] Patent: WO2015/131080, 2015, A1. Location in patent: Paragraph 001135; 001136
[4] Journal of Heterocyclic Chemistry, 1986, vol. 23, p. 53 - 57
[5] Journal of Organic Chemistry, 1952, vol. 17, p. 407,412
