N-(3-Formyl-2-pyridinyl)-2,2-dimethylpropanamide → HCID 178517374, compound

Temperature

-78 °C

To a cooled solution (−78° C.) of LDA (2.0 M, 251 mmol) in 600 mL THF was added ester 4-3 (prepared from cyclopropylacetic acid and methanolic HCl solution, 15 g, 131 mmol) gradually over 30 min. The reaction mixture was stirred for 30 min at −78° C. Aldehyde 4-2 (22.5 g, 109 mmol) in 40 mL THF was added. The reaction mixture was stirred at −78° C. for 1 hr, then was warmed up to room temperature over 1 hr and quenched with 200 mL NH4Cl (sat.). The mixture was extracted with ethyl acetate (×3). The combined organic layers were washed with water, brine and dried over MgSO4 and concentrated to give a viscous residue which was subsequently dissolved in 200 mL 3N HCl. The mixture was refluxed at 105° C. for 24 hr. After concentration, the residue was poured into 500 mL ice-water and quenched with K2CO3 gradually (pH=9) to yield a solid as the desired product 4-4, which was filtered and dried in vacuum.

1. stirringThe reaction mixture was stirred at −78° C. for 1 hr
2. temperaturewas warmed up to room temperature over 1 hr
3. customquenched with 200 mL NH4Cl (sat.)
4. extractionThe mixture was extracted with ethyl acetate (×3)
5. washThe combined organic layers were washed with water, brine
6. dry with materialdried over MgSO4
7. concentrationconcentrated
8. customto give a viscous residue which
9. temperatureThe mixture was refluxed at 105° C. for 24 hr
10. concentrationAfter concentration
11. additionthe residue was poured into 500 mL ice-water
12. customquenched with K2CO3 gradually (pH=9)

ORD record

ord-03adb84dbbfc4012a83165ba453fe7fd

Source dataset

uspto-grants-2002_06

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06410526B1