4-Methylpyrimidine → 1-(Pyrimidin-4-yl)propan-2-one

Temperature

-78 °C

4-Methylpyrimidine (2 g) was stirred in dry tetrahydrofuran (65 ml) under argon and the solution was cooled to −78° C. Lithium diisopropylamide (13.8 ml, 2M solution) was added dropwise over 20 minutes and stirring was continued at −78° C. for 1.5 h before dropwise addition of N-methoxy-N-methylacetamide (2.49 ml). The reaction mixture was stirred at −78° C. for a further 40 minutes before allowing to warm to room temperature over 1.25 h, then partitioned between saturated aqueous sodium carbonate and ethyl acetate. The layers were separated and the aqueous phase further extracted with ethyl acetate. The combined extracts were washed with brine, dried (MgSO4), filtered and evaporated. The residue was purified by column chromatography on silica gel eluting with 40-50% ethyl acetate in hexane to give an oil which crystallised on standing (0.70 g, 24%).

1. stirringThe reaction mixture was stirred at −78° C. for a further 40 minutes
2. temperatureto warm to room temperature over 1.25 h
3. custompartitioned between saturated aqueous sodium carbonate and ethyl acetate
4. customThe layers were separated
5. extractionthe aqueous phase further extracted with ethyl acetate
6. washThe combined extracts were washed with brine
7. dry with materialdried (MgSO4)
8. filtrationfiltered
9. customevaporated
10. customThe residue was purified by column chromatography on silica gel eluting with 40-50% ethyl acetate in hexane
11. customto give an oil which
12. customcrystallised

ORD record

ord-f04b961bfe6e4fb984c98e45a5869068

Source dataset

uspto-grants-2008_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07358376B2