Methylamine → N-methyl-1-(4-((triisopropylsilyloxy)methyl)thiazol-2-yl)methanamine

Participants

Reaction Steps

To a solution of 4-((triisopropylsilyloxy)methyl)thiazole (2 g, 7.367 mmol) in diethyl ether solution (30 mL) at −78° C. was added butyl lithium (1.6 M in hexanes, 5.1 mL). The resulting solution was stirred at the same temperature for one hr, dimethylformate (1.14 mL, 14.734 mmol) was added to the light yellow reaction mixture. The reaction was warmed to room temperature and stirred for 3 hr, then quenched with water, extracted with ethyl acetate three times. The combined organic layers were washed with brine, dried with anhydrous Na2SO4, concentrated to a residue which was not purified and identified for the next step. Methylamine (2 M solution in methanol, 10 mL) in the flask at 0° C. was added titanium isopropoxide (2.55 mL, 8.692 mmol) and stirred for 20 minutes, then the above crude aldehyde was added to the reaction and stirred for 3 hr. The reaction mixture was added sodium borohydrate (354 mg, 9.36 mmol) portionwise. After overnight the reaction solvent was removed, diluted with DCM/water. The resulting precipitate was filtered through a celite. The clear liquid was extracted with chloroform three times, dried with anhydrous Na2SO4, concentrated to a residue which was purified by flash column to give N-methyl-1-(4-((triisopropylsilyloxy)methyl)thiazol-2-yl)methanamine (1.37 g). 1H NMR (300 MHz, CDCl3), d: 7.197 (s, 1H), 4.975 (s, 2H), 4.075 (s, 2H), 2.555 (s, 3H), 1.196 (m, 3H), 1.134 (d, J=5.7 Hz, 18H).

Provenance & Evidence