Methyl iodide → 2-chloro-N,N,5-trimethylnicotinamide

Temperature

-90 °C

A solution of 2-chloro-5-iodo-N,N-dimethylnicotinamide (0.385 g, 1.24 mmol), prepared as in Example 14, in 10 mL of THF was distilled to remove volatile gases. The residual solution was cooled -90° C. and then tert-butyllithium (1.9 mL, 2.48 mmol) was added over 3 to 5 minutes. Iodomethane (0.23 mL, 3.72 mmol) was added and the mixture was allowed to warm to room temperature. The mixture was partitioned between aqueous sodium carbonate (pH 10) and hexanes and the aqueous layer was extracted with ethyl acetate. The extract was washed with brine, dried (Na2 SO4) and concentrated. The residue was purified on silica gel by column chromatography eluting with hexanes/ethyl acetate (3:1) to give 2-chloro-N,N,5-trimethylnicotinamide (0.152 g, 0.78 mmol), m.p. 117°-119° C.

1. distillationin 10 mL of THF was distilled
2. customto remove volatile gases
3. temperatureto warm to room temperature
4. customThe mixture was partitioned between aqueous sodium carbonate (pH 10) and hexanes
5. extractionthe aqueous layer was extracted with ethyl acetate
6. washThe extract was washed with brine
7. customdried (Na2 SO4)
8. concentrationconcentrated
9. customThe residue was purified on silica gel by column chromatography
10. washeluting with hexanes/ethyl acetate (3:1)

ORD record

ord-208a410d6dca4634a832119e831d380e

Source dataset

uspto-grants-1997_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US05688795