Diisopropylamine → 4-Chloropyridine-3-carbaldehyde

Temperature

0 °C

35.8 ml of n-BuLi (1.6 M in hexane; 57 mmol, 1 eq.) is added to a solution of 7.5 ml of N,N-diisopropylamine in 100 ml of tetrahydrofuran at −60° C. in nitrogen. The mixture is then left under stirring at 0° C. for 45 min before being cooled to −90° C. To this solution, a solution of 6.5 g of 4-chloropyridine (57 mmol, 1 eq.) in 25 ml of tetrahydrofuran is added drop by drop such that the temperature remains between −70 and −60° C. The mixture is left under stirring at −70° C. for 3 hrs. Then, a solution of 5.1 ml of ethylformate (63 mmol, 1.1 eq.) in 10 ml of tetrahydrofuran is added. The mixture is left under stirring for 1 hr at −65/−70° C. and the reaction mixture is then returned to −10° C. and hydrolysed with water. The organic phase is separated and the aqueous phase is extracted 3 times with ethyl acetate. The combined organic phases are dried on Na2SO4 and the solvent is evaporated.

1. waitThe mixture is then left
2. temperaturebefore being cooled to −90° C
3. customremains between −70 and −60° C
4. waitThe mixture is left
5. stirringunder stirring at −70° C. for 3 hrs
6. waitThe mixture is left
7. stirringunder stirring for 1 hr at −65/−70° C.
8. customThe organic phase is separated
9. extractionthe aqueous phase is extracted 3 times with ethyl acetate
10. customThe combined organic phases are dried on Na2SO4
11. customthe solvent is evaporated

ORD record

ord-3f124969a07d4c7db05a18516d726f02

Source dataset

uspto-grants-2008_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07456192B2