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

Participants

Reaction Conditions

Reaction Steps

To a suspension of 4-(2-chlorothieno[3,2-d]pyrimidin-4-yl)morpholine 4 (50 g, 195 mmol, 1.0 equiv.) in THF (anhydrous, 800 ml) at −78° C. was added slowly 2.5 M solution of n-BuLi in hexanes (93.9 ml, 234.6 mmol, 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, 22.7 ml, 293 mmol, 1.5 equiv.) was added slowly. The resulting solution was stirred at −78° C. for 0.5 hour, then 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 (1.65 L) and ice water (800 ml). The resulting slurry was stirred at 0-10° C. for 0.5 hour, filtered and rinsed with cold water (200 ml). The cake was dried in vacuum oven at 40° C. for 24 hours to afford 2-chloro-4-morpholinothieno[3,2-d]pyrimidine-6-carbaldehyde 5 as a light yellow solid (54.9 g, 99% yield). 1H NMR (400 MHz, DMSO-d6) δ 3.76 (t, J=4.9 Hz, 1H), 3.95 (t, J=4.9 Hz, 4H), 8.28 (s, 1H), 10.20 (s, 1H). LCMS (ESI pos) m/e 285 (M+1).

Provenance & Evidence