Iodine → (R)-5-tert-butyl-3-((tetrahydrofuran-2-yl)methyl)thiazol-2(3H)-imine hydroiodide

Participants

Reaction Steps

To a solution of 3,3-dimethylbutanal (9.90 g, 99 mmol) in acetonitrile (60 mL) were added molecular sieves (8 g) and (R)-(tetrahydrofuran-2-yl)methanamine (10 g, 99 mmol). The reaction mixture was stirred at room temperature for 24 hours and then filtered through celite. To the filtrate was added potassium thiocyanate (12.78 g, 131 mmol). The temperature was adjusted to 50° C. and the mixture was stirred until the solids were dissolved. Then, iodine (25.09 g, 99 mmol) was added to the mixture and stirred at 50° C. for 24 hours. The reaction mixture was cooled, and to the mixture was added sodium meta-bisulfite 20% (100 mL) and stirred for 30 min. The organic layers were separated and the aqueous layer was washed with dichloromethane (3×40 mL). The combined organic extracts were dried with sodium sulfate, filtered and concentrated to obtain the crude product as a yellow solid. The residue was taken into dichloromethane (20 mL) and ethyl acetate (80 mL), the mixture was warmed to 40° C., sonicated, and cooled to between 0-10° C. The solid was collected and washed with cold ethyl acetate to obtain the title compound (18.2 g, 50%). 1H NMR (300 MHz, DMSO-d6) δ ppm 1.27 (s, 9 H) 1.48-1.61 (m, 1 H) 1.78-1.93 (m, 2 H) 1.94-2.07 (m, 1 H) 3.62-3.71 (m, 1 H) 3.76-3.84 (m, 1 H) 3.92-4.08 (m, 2 H) 4.11-4.20 (m, 1 H) 7.19 (s, 1 H) 9.39 (s, 2 H); MS (DCI/NH3) m/z 241 (M+H)+.

Provenance & Evidence