N,N,N',N'-Tetramethylethylenediamine → tert-butyl 3-(2-chloro-9-methyl-6-morpholino-9H-purin-8-yl)-3-hydroxypiperidine-1-carboxylate

Participants

Reaction Conditions

Reaction Steps

To a stirred solution of 4-(2-chloro-9-methyl-9H-purin-6-yl)morpholine (5.0 g) and N,N,N′,N′-tetramethylethylenediamine (4.46 mL) in tetrahydrofuran (80 mL) at −78° C. was added 2.5 M of n-Butyllithium in THF (17 mL). The solution was stirred at −78° C. for 15 mins then the temp was raised to −40° C. until the solution became clear and dark red (indicating full lithiation). The solution was lowered back to −78° C. and tert-butyl 3-oxopiperidine-1-carboxylate (8.64 g) in 10 mL THF was added slowly over 5 minutes and stirred for 1.5 hrs then quenched with water. The reaction mixture was diluted with ethyl acetate and extracted with a saturated ammonium chloride solution. The organic layer was dried, filtered and concentrated. Any remaining starting material was removed by trituration with hot ether to afford the crude product tert-butyl 3-(2-chloro-9-methyl-6-morpholino-9H-purin-8-yl)-3-hydroxypiperidine-1-carboxylate as an orange oil in quantitative yield.

Provenance & Evidence