Hydrochloric Acid → 2,4-Dichloropyrimidine-5-carbaldehyde

Temperature

-78 °C

A solution of isopropyl magnesium chloride lithium chloride complex in THF (2M, 184 mL, 368 mmol) was added drop-wise over about 30 min to a 2 L round-bottomed flask charged with a solution of 5-bromo-2,4-dichloropyrimidine (49.6 g, 218 mmol) in THF (1000 mL) at about −78° C. The reaction was allowed to stir at about −78° C. for about 30 min. Morpholine-4-carbaldehyde (75.0 g, 653 mmol) was then added drop-wise at about −78° C. over about 30 min. The reaction was allowed to stir for about 30 min at about −78° C. then allowed to warm to about −35° C. and stirred for about 30 min. Aqueous HCl (1N, 250 mL) and Et2O (500 mL) were added and the reaction mixture was allowed to warm to ambient temperature. The organic layer was separated and the aqueous layer was further extracted with Et2O (200 mL). The combined organic layers were dried over anhydrous MgSO4, filtered through a silica gel pad on a fritted funnel, and concentrated under reduced pressure. The crude material was purified by silica gel chromatography using DCM (100%) as the eluent to provide 2,4-dichloropyrimidine-5-carbaldehyde (27.3 g, 71%) as a light yellow solid. 1H NMR (400 MHz, CDCl3) δ 10.34 (s, 1H), 9.30 (s, 1H).

1. stirringto stir for about 30 min at about −78° C.
2. temperatureto warm to about −35° C.
3. stirringstirred for about 30 min
4. temperatureto warm to ambient temperature
5. customThe organic layer was separated
6. extractionthe aqueous layer was further extracted with Et2O (200 mL)
7. dry with materialThe combined organic layers were dried over anhydrous MgSO4
8. filtrationfiltered through a silica gel pad on a fritted funnel
9. concentrationconcentrated under reduced pressure
10. customThe crude material was purified by silica gel chromatography

ORD record

ord-dfdc5ce8d7964fc79652a427427c82fb

Source dataset

uspto-grants-2014_01

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08637529B2