Dimethylformamide → HCID 59406942, compound

Temperature

-30 °C

A solution of 51 ml (128 mmol) of 2.5 N n-butyllithium in hexanes was added slowly to a THF solution of 16 ml (95 mmol) of tetramethylpiperidine cooled in a dry ice-acetone bath. The solution was warmed to −30° C. and cooled to −60° C. before 5.0 g (32 mmol) of 6-chloronicotinic acid was added portion wise. The mixture was warmed to −25° C. and stirred for 30 min. It was then cooled to −70° C. and 10 ml (129 mmol) DMF was added quickly. After quenching with 1N HCl, the solution was warmed to room temperature. The pH was brought to about 4 with additional 1N HCl and the solution was continuously extracted with EtOAc overnight. The EtOAc was dried (MgSO4) and concentrated. The residue was dissolved in 100 ml EtOH and 2 ml concentrated H2SO4 was added. The solution was heated at reflux for 24 h. The mixture was brought to about pH=4 with 50% NaOH and was extracted twice with ether. The ether was dried (MgSO4) and concentrated to gave an oil that was chromatographed on silica gel (50% hexanes in CH2Cl2 with gradient elution to 100% CH2Cl2) to afford 1 g of product as an oil that slowly solidified. NMR (CDCl3): 1.4 (t, 3H), 4.5 (q, 2H), 7.7 (s, 1H), 9.1 (s, 1H), 10.7 (s, 1H).

1. temperaturecooled in a dry ice-acetone bath
2. additionwas added portion wise
3. temperatureThe mixture was warmed to −25° C.
4. temperatureIt was then cooled to −70° C.
5. customAfter quenching with 1N HCl
6. temperaturethe solution was warmed to room temperature
7. extractionthe solution was continuously extracted with EtOAc overnight
8. dry with materialThe EtOAc was dried (MgSO4)
9. concentrationconcentrated
10. dissolutionThe residue was dissolved in 100 ml EtOH
11. addition2 ml concentrated H2SO4 was added
12. temperatureThe solution was heated
13. temperatureat reflux for 24 h
14. extractionwas extracted twice with ether
15. dry with materialThe ether was dried (MgSO4)
16. concentrationconcentrated
17. customto gave an oil that
18. customwas chromatographed on silica gel (50% hexanes in CH2Cl2 with gradient elution to 100% CH2Cl2)

ORD record

ord-a2d500ffefa641418b25ec501fb08b4d

Source dataset

uspto-grants-2013_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08399489B2