Sodium Carbonate → tert-butyl 2-amino-4H,5H,6H,7H-[1,3]thiazolo[5,4-c]pyridine-5-carboxylate

Participants

Reaction Steps

To a solution of compound tert-butyl 4-oxopiperidine-1-carboxylate (24.0 g, 120.6 mmol) in dry CHCl3 (500 mL) at 0-5° C., was slowly added a solution of Br2 in CHCl3 (100 mL) over 1.5 hours. The reaction mixture was warmed to RT and stirred for 3 hours. The reaction mixture was concentrated to obtain solid, which was thoroughly washed with Et2O. The resulting intermediate tert-butyl 3-bromo-4-oxopiperidine-1-carboxylate was used immediately in the next reaction. Accordingly, this intermediate (20 g, 72 mmol) was suspended in pentane, filtered, washed with pentane, and the solid so obtained dried in vacuo and dissolved in EtOH (100 mL). Thiourea (5.46 g, 72.0 mmol) was added and the reaction mixture heated for 4 hours at 70-75° C. The reaction mixture was concentrated to yield a residue, which was treated with aq. Na2CO3 solution, adjusted to pH=10, extracted with EtOAc, washed with water, washed with brine solution, dried (Na2SO4), filtered, and concentrated. The residue washed with pentane to obtain tert-butyl 2-amino-6,7-dihydrothiazolo[5,4-c]pyridine-5(4H)-carboxylate (8.7 g, 28% yield)

Provenance & Evidence