Hydrochloric Acid → HCID 59511925, compound

Participants

Reaction Steps

Cool a solution of 5-bromopyrimidine (7.63 g, 48.0 mmol) in tetrahydrofuran (375 mL) to −100° C., and add slowly n-butyllithium (2.5 M in hexanes, 17.8 mL, 44.5 mmol), keeping the temperature below −90° C. Stir the reaction for 30 min at −100° C. Cool a solution of 1-(tert-butoxycarbonyl)-2-pyrrolidinone (8.08 g, 43.6 mmol) in tetrahydrofuran (100 mL) to −78° C. and add to the reaction mixture with a cannula. Stir the reaction at −100° C. for 30 min, then add a 2 M solution of hydrogen chloride in diethyl ether (25 mL, 50 mmol). Allow the reaction to warm to room temperature and add dichloromethane (500 mL) and water (500 mL). Separate the layers and extract the aqueous layer with dichloromethane (2×250 mL). Combine the organic portions and wash with brine (400 mL), dry over magnesium sulfate, filter, and evaporate under reduced pressure to afford a crude mixture (10.98 g). Purify by flash chromatography (two stacked 120 g RediSep silica gel columns, 0:100 to 30:70 gradient of [90:10:1 dichloromethane:methanol:concentrated ammonium hydroxide]:dichloromethane) to provide an impure mixture containing the product (5.35 g, ˜35%) which is used without further purification. MS (APCI+): 148 [C13H19N3O3—C5H8O2—H2O+H]+; 1H NMR (300 MHz, CDCl3): δ 9.36 (s, 1H), 9.22 (s, 2H), 4.63 (br s, 1H), 3.19-3.29 (m, 2H), 3.04 (t, J=7.0 Hz, 2H), 1.97 (quintet, J=6.8 Hz, 2H), 1.41 (s, 9H).

Provenance & Evidence