Sodium Iodide → HCID 19963296, compound

Participants

Reaction Steps

(4-Fluorophenyl)(thiazol-5-yl)methanol from step (i) was reduced with trimethylsilyliodide using a slight modification of 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 (6.78 g, 47.8 mmol) and acetonitrile (10 mL). Then, chlorotrimethylsilane (6.0 mL, 48 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)(thiazol-5-yl)methanol (2.00 g, 9.56 mmol) in acetonitrile (40 mL) and dichloromethane (50 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 heated to 40° C. for 72 h. Then the solution was cooled back down to 5° C. for work-up. A solution of NaOH (5 N, 10 mL, 50 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 10-30% EtOAc/hexanes to afford the product (1.26 g, 6.50 mmol, 68% yield). MS (M+H)+ 194.

Provenance & Evidence