Hydrochloric Acid → 2-Chloro-4-morpholinothieno[2,3-d]pyrimidine-6-carbaldehyde

Participants

Reaction Conditions

Reaction Steps

To a suspension of 4-(2-chlorothieno[2,3-d]pyrimidin-4-yl)morpholine 18 (90.2 g, 0.350 mol, 1.0 equiv.) in THF (anhydrous, 1400 ml) at −78° C. was added slowly 2.5 M solution of n-BuLi in hexanes (169 ml, 0.522 mol, 1.2 equiv.). The resulting slurry was allowed to warm up to −60° C. and a clear brown solution was observed. The solution was then cooled to −78° C. and DMF (anhydrous, 38.67 g, 0.530 mole, 1.5 equiv.) was added slowly. The resulting solution was stirred at −78° C. for 0.5 hour, and warmed up slowly to 0° C. over a period of 1-1.5 hours. The solution was then poured slowly to a mixture of 0.25 M aq. hydrochloric acid (3.0 L) and ice water (1.4 L). The resulting slurry was stirred at 0-10° C. for 0.5 hour, filtered and rinsed with cold water (0.5 L). The cake was dried in vacuum oven at 55° C. for 24 hours to afford 2-chloro-4-morpholinothieno[2,3-d]pyrimidine-6-carbaldehyde 19 as a light yellow solid (90.8 g, 91% yield). 1H NMR (400 MHz, DMSO-d6) δ 3.778 (t, J=4.8 Hz, 4H), 3.990 (t, J=4.8 Hz, 4H), 8.756 (s, 1H), 10.022 (s, 1H). LCMS (ESI pos) m/e 285 (M+1).

Provenance & Evidence