Dimethyl Sulfoxide → 2-Chloro-4-pyridinecarboxaldehyde

Temperature

-78 °C

In a 250 mL tricol equipped with a low temperature thermometer and two equalizing dropping funnels was charged oxalyl dichloride (1.24 g, 9.81 mmol) in dichloromethane (15 mL) and this solution was stirred under N2 at −78° C. The first equalizing dropping funnel was connected to a nitrogen flow line and was charged with a solution of (2-chloropyridin-4-yl)methanol SLA 07152 (0.94 g, 6.54 mmol) with dichloromethane (15 mL). The other was charged with a solution of dimethyl sulfoxide anhydrous (1.7 mL, 19.63 mmol) in dichloromethane (2 mL) and this solution was added dropwise (25 min) in order to stabilize the temperature between −60° C. and −70° C. At the end of the addition the reaction solution was warmed to −60° C. over a period of 20 min then the solution of (2-chloropyridin-4-yl)methanol SLA 07152 was added dropwise (50 min) keeping the temperature between −50° C. and −60° C. in the reactor then the mixture reaction was warmed to −45° C. over a period of 30 min. The dropping funnel was washed with dichloromethane (2×5 mL) and charged with a solution of triethylamine (480 μl, 6.51 mmol) in dichloromethane (4 mL) which was added (10 min) to the reaction mixture and finally the reaction flask was allowed to warm to 0° C. over 10 min. The reaction solution was transferred to a 500 mL separatory funnel charged with 130 mL of a 5% aqueous NH4Cl solution. The two phases were separated the aqueous phase was extracted with dichloromethane (3×50 mL) and the combined organic phases were washed with 1 M aqueous phosphate buffer (pH=7; 4×100 mL), then dried over MgSO4, filtered and evaporated. 2-Chloropyridine-4-carbaldehyde SLA 07156 was obtained as an orange solid (0.740 g, 76% yield).

1. customIn a 250 mL tricol equipped with a low temperature thermometer and two
2. additionthis solution was added dropwise (25 min) in order
3. customthe temperature between −60° C. and −70° C
4. additionAt the end of the addition the reaction solution
5. temperaturewas warmed to −60° C. over a period of 20 min
6. customthe temperature between −50° C. and −60° C.
7. customthe mixture reaction
8. temperaturewas warmed to −45° C. over a period of 30 min
9. washThe dropping funnel was washed with dichloromethane (2×5 mL)
10. additionwas added (10 min) to the reaction mixture
11. temperatureto warm to 0° C. over 10 min
12. customThe reaction solution was transferred to a 500 mL separatory funnel
13. customThe two phases were separated the aqueous phase
14. extractionwas extracted with dichloromethane (3×50 mL)
15. washthe combined organic phases were washed with 1 M aqueous phosphate buffer (pH=7; 4×100 mL)
16. dry with materialdried over MgSO4
17. filtrationfiltered
18. customevaporated

ORD record

ord-5061700a79904ceabf6ac38ac16ba30b

Source dataset

uspto-grants-2015_01

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08927589B2