Ethyl 2-methylnicotinate → HCID 58745978, compound

Temperature

0 °C

To a clear solution of 2-methyl-nicotinic acid ethyl ester (50.6 g, 306 mmol) in anhydrous methylene chloride (200 mL) was added O-mesitylenesulfonylhydroxylamine (73 g, 337 mmol; prepared according to a literature procedure described in Krause; J. G., Synthesis 1972, 140); in portions at 0° C. The solution obtained was stirred at 0° C. for 15 min, and then at rt for 1 h. Concentration under reduced pressure gave a yellow solid. After the solid was dissolved in anhydrous DMF (300 mL), N,N-dimethylformamide dimethyl acetal (122 mL, 918 mmol) was added at 0° C. The mixture was stirred at 0° C. for 15 min, and then at 90° C. for 3 h. The reaction mixture was concentrated under reduced pressure, mixed with H2O (200 mL), and extracted with Et2O (3×180 mL). The combined organic solutions were washed sequentially with brine (50 mL), 1N aqueous HCl (50 mL), and brine (50 mL), and dried over Na2SO4. Filtration through a SiO2 column, which was then eluted with 30% EtOAc in heptane, gave compound 777A (43.3 g, 74%) as a yellow solid. HPLC: 80% at 3.20 min (retention time) plus 20% corresponding methyl ester at 2.83 min (retention time) (YMC S5 ODS-A column 4.6×50 mm eluting with 10-90% aqueous methanol over 4 min containing 0.2% phosphoric acid, 4 mL/min, monitoring at 220 nm). MS (ES): m/z 191 [M+H]+.

1. customprepared
2. custom, Synthesis 1972, 140)
3. customat 0° C
4. customThe solution obtained
5. waitat rt for 1 h
6. concentrationConcentration under reduced pressure
7. customgave a yellow solid
8. stirringThe mixture was stirred at 0° C. for 15 min
9. waitat 90° C. for 3 h
10. concentrationThe reaction mixture was concentrated under reduced pressure
11. additionmixed with H2O (200 mL)
12. extractionextracted with Et2O (3×180 mL)
13. washThe combined organic solutions were washed sequentially with brine (50 mL), 1N aqueous HCl (50 mL), and brine (50 mL)
14. dry with materialdried over Na2SO4
15. filtrationFiltration through a SiO2 column, which
16. washwas then eluted with 30% EtOAc in heptane

ORD record

ord-38200c1c81d84e10a7546c860836002d

Source dataset

uspto-grants-2010_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07655689B2