Sodium Iodide → HCID 57428858, compound

Participants

Reaction Steps

(4-Fluorophenyl)(3-(2-(pyrrolidin-1-yl)ethyl)thiophen-2-yl)methanol from step (ii) was reduced with trimethylsilyliodide in accordance with published procedure (See reference: Tetrahedron 1995, 51 (41), 11043-11062.) A dry three-necked flask equipped with an addition funnel and a nitrogen inlet was charged with sodium iodide (0.87 g, 5.8 mmol) and acetonitrile (5.0 mL). Then, chlorotrimethylsilane (0.73 mL, 5.8 mmol) was added via syringe and the reaction mixture was allowed to stir at ambient temperature for about 15 min. At that time, the bright yellow mixture was cooled to 0° C. and a solution of (4-fluorophenyl)(3-(2-(pyrrolidin-1-yl)ethyl)thiophen-2-yl)methanol (353 mg, 1.16 mmol) in acetonitrile (5 mL) was added dropwise over the course of an hour. The reaction mixture was allowed to warm to room temperature over 16 h and then cooled back down below 5° C. before work-up. A solution of NaOH (5 N, 1.5 mL, 7.5 mmol) was added and the reaction mixture cooled to rt before it was diluted with EtOAc and stirred for an additional 10 min. The layers were separated and the aqueous layer extracted with another portion of EtOAc. The combined organic layers were washed with a solution of saturated aqueous Na2S2O3.5H2O, water, and brine, dried over MgSO4, and concentrated. The resulting residue was purified by flash chromatography, eluting with 1-10% (0.5 M ammonia in MeOH)/dichloromethane to afford the product as a pale yellow oil (160 mg, 0.56 mmol, 48% yield). MS (M+H)+ 290.

Provenance & Evidence