Ethyl formate → 2-Chloro-4-methoxypyrimidine-5-carbaldehyde

Temperature

0 °C

2,2,6,6-Tetramethylpiperidine (2.7 ml, 2.25 g, 16.0 mmol) was added to a solution of n-butyl lithium (n-BuLi) (10 ml, 16.0 mmol, 1.6M in hexanes) in tetrahydrofuran (THF) (100 ml) at -78° C. The solution was allowed to warm to 0° C. and stirred for 45 minutes, cooled to -78° C. and 2-chloro-4-methoxypyrimidine (726 mg, 5.04 mmol) in THF (20 ml) was added dropwise. The solution was then stirred for 1 hour. Then, ethyl formate (0.50 ml, 0.46 g, 6.2 mmol) in THF (20 ml) was added dropwise and the solution was stirred for 1.5 hours. The reaction mixture was quenched with acetic acid (HOAc) (conc.) at -78° C., diluted with water and extracted with ethyl acetate (EtOAc) (3 times). The combined extracts were washed with saturated brine, dried (MgSO4), filtered and concentrated in vacuo to give 1.06 g of crude material. Preparative radial chromatography (SiO2 ; hexane/EtOAc gradient elution) afforded 420 mg (48%) of 2-chloro-4-methoxypyrimidine-5-carboxaldehyde.

1. temperaturecooled to -78° C.
2. stirringThe solution was then stirred for 1 hour
3. stirringthe solution was stirred for 1.5 hours
4. customThe reaction mixture was quenched with acetic acid (HOAc) (conc.) at -78° C.
5. additiondiluted with water
6. extractionextracted with ethyl acetate (EtOAc) (3 times)
7. washThe combined extracts were washed with saturated brine
8. dry with materialdried (MgSO4)
9. filtrationfiltered
10. concentrationconcentrated in vacuo
11. customto give 1.06 g of crude material
12. washPreparative radial chromatography (SiO2 ; hexane/EtOAc gradient elution)

ORD record

ord-c470ab0e6a314aee943f366b5c4b413e

Source dataset

uspto-grants-1998_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US05714438