Sodium Chloride → 1-methyl-2,3-dihydro-1H-inden-2-one

Participants

Reaction Conditions

Reaction Steps

A solution of 1-(1H-inden-2-yl)pyrrolidine (1.00 g, 5.40 mmol) in anhydrous 2-methyltetrahydrofuran (13.3 mL) was cooled to −55° C. and treated with a solution of n-BuLi (1.6 M in hexanes, 4.0 mL, 6.4 mmol) dropwise. The mixture was then stirred at −55° C. for 15 min. Iodomethane (0.4 mL, 6.3 mmol) was added and, after stirring for 5 min, the mixture was quenched by addition of 1 N HCl (6.7 mL). The solvent was removed in vacuo, water (17 mL) was added and the mixture was heated at reflux for 10 min. The mixture was then cooled to ambient temperature and extracted with diethyl ether. The organic layer was washed with brine, and the combined aqueous layers were saturated with NaCl and extracted twice more with diethyl ether. The combined organic extracts were dried (Na2SO4), filtered and concentrated to give an oil, which was treated with TFA (2.5 mL) in CH2Cl2 (2.5 mL) for 5 min. The mixture was concentrated in vacuo and the residue purified by reverse phase preparative HPLC eluting with a gradient of 90:10 to 0:100 A:B where A=0.1% TFA in H2O and B=0.1% TFA in CH3CN). The fractions containing product were combined and concentrated to give an aqueous residue which was saturated with NaCl and extracted with EtOAc (3×). The combined organic extracts were dried (Na2SO4), filtered and concentrated in vacuo to give the title compound. MS: m/z=147.1 (M+1).

Provenance & Evidence