Formic Acid → 2-Chloro-6-formylaminomethylnicotinic acid methyl ester

To a solution of 2-chloro-6-diformylaminomethylnicotinic acid methyl ester (53.0 g, 0.21 mol) in methanol (300 mL) was added water (3.72 mL, 0.21 mol) and formic acid (15.6 mL, 0.42 mol) before the reaction mixture was heated at reflux for 16 hours. The reaction mixture was concentrated in vacuo and the residue dissolved in ethyl acetate (200 mL). The resultant solution was washed with water (200 mL) and the aqueous layer extracted with ethyl acetate (2×100 mL). The combined organic extracts were washed with brine (100 mL), dried (MgSO4) and concentrated in vacuo to yield the title compound as an orange oil which solidified on standing (42.6 g, 90%). 1H NMR (CDCl3, 400 MHz) 8.34 (1H, s), 8.17 (1H, d, J=8.0 Hz), 7.31 (1H, d, J=7.8 Hz), 6.63 (1H, br s), 4.63 (2H, d, J=5.6 Hz), 3.96 (3H, s).

1. temperaturewas heated
2. temperatureat reflux for 16 hours
3. concentrationThe reaction mixture was concentrated in vacuo
4. dissolutionthe residue dissolved in ethyl acetate (200 mL)
5. washThe resultant solution was washed with water (200 mL)
6. extractionthe aqueous layer extracted with ethyl acetate (2×100 mL)
7. washThe combined organic extracts were washed with brine (100 mL)
8. dry with materialdried (MgSO4)
9. concentrationconcentrated in vacuo

ORD record

ord-53fd8f7e09ca40a684f3410359717da5

Source dataset

uspto-grants-2012_10

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08288408B2