反应详情

温度

13 °C

A solution of 2.1 M isopropylmagnesium chloride in tetrahydrofuran (555.3 g, 1.20 mol) was added over 1.5 hours to the crude solution of 2-(trimethylacetylamino)-6-bromopyridine in toluene (501.2 g of crude solution from previous step, 0.500 mol) maintaining the temperature below 3° C. The resulting mixture was aged at 5° C. for 24 hours. Dimethylformamide (112.3 g, 1.54 mol) was added over 20 min maintaining the temperature at 11-15° C. After 15 min, the solution was transferred into 1 L of 10% aqueous acetic acid and the biphasic mixture stirred for 30 min. The organic phase was separated and combined with 500 mL of 20 wt % aqueous sodium hydrogen sulfite. The biphasic mixture was stirred vigorously for 45 min. The aqueous layer was separated and treated with 500 mL of 20 wt % aqueous Na2CO3, then extracted with ethyl acetate (2×500 mL). The combined organic layers were concentrated to approximately 400 mL at 50° C., 600 mmHg. The concentrate was dried over 8 g of MgSO4 and filtered to give 363.7 g of yellow solution (25.65 wt % title aldehyde, 93.28 assay g).

1. temperaturemaintaining the temperature below 3° C
2. waitAfter 15 min
3. customThe organic phase was separated
4. stirringThe biphasic mixture was stirred vigorously for 45 min
5. customThe aqueous layer was separated
6. additiontreated with 500 mL of 20 wt % aqueous Na2CO3
7. extractionextracted with ethyl acetate (2×500 mL)
8. concentrationThe combined organic layers were concentrated to approximately 400 mL at 50° C.
9. dry with materialThe concentrate was dried over 8 g of MgSO4
10. filtrationfiltered