Tert-Butylamine → 1-(Tert-butylamino)isoquinoline-7-carboxylic acid

Participants

Reaction Conditions

Reaction Steps

To a suspension of 1-chloroisoquinoline-7-carboxylic acid (100 mg, 0.482 mmol), RuPhos (6.5 mg, 0.014 mmol), BrettPhos (11.2 mg, 0.014 mmol) and sodium tert-butoxide (70.2 mg, 0.723 mmol) in dioxane (0.5 mL) was added t-butylamine (0.254 mL, 2.41 mmol). The vessel was sealed and mixture was heated to 110° C. and stirred overnight. The reaction was cooled down to room temperature and lithium bistrimethylsilylamide (0.136 mL, 0.723 mmol) was added. The reaction mixture was heated to 110° C. and left stirring overnight. The reaction mixture was cooled down to room temperature and filtered through celite and rinsed with methanol. The filtrate was concentrated under reduced pressure and 1N aqueous sodium hydroxide (1 mL) was added. Partitioned between ethyl acetate and a mixture of water and 1N aqueous sodium hydroxide. The layers were separated and the aqueous layer was acidified to pH 4. The aqueous layer was extracted into ethyl acetate. The extracts were dried over magnesium sulfate, filtered and concentrated under reduced pressure to obtain 1-(tert-butylamino)isoquinoline-7-carboxylic acid.

Provenance & Evidence