Acetic Acid → 3,4-Dichloropyridine-2-carboxamide

온도

-78 °C

To a solution of 2,2,6,6-tetramethylpiperidine (31.1 g, 0.22 mol) in diethyl ether (400 mL) at 0° C. was added n-BuLi in hexane (1.6 M, 138.0 mL, 0.22 mol) via syringe over 15 min. The resulting solution was stirred at 0° C. for 0.5 h and at −78° C. for 0.5 h. To this mixture was then slowly added a solution of 3,4-dichloropyridine (29.6 g, 0.20 mol) in diethyl ether (20 mL) via syringe over 15 min. The resulting mixture was stirred at −78° C. for 2 h before the addition of isocyanatotrimethylsilane (85% pure, 40.0 mL, 0.30 mol). The source for isocyanatotrimethylsilane is TCI. After the addition, the cooling bath was removed and the reaction mixture was allowed to warm to room temperature over 1 h. The reaction mixture was quenched with acetic acid (40 g, 0.67 mol) and 200 mL of water. The mixture was allowed to stir overnight and the white solid that formed was collected through filtration and washed with water. The filtrate was extracted with ethyl acetate (3×300 mL). The solid that was collected previously was dissolved in the combined organic layers, and the resulting solution was washed with brine (2×200 mL), dried over MgSO4 and concentrated in vacuo. The residue was suspended in 200 mL of diethyl ether and sonicated. The remaining solid was collected through filtration and washed with minimum amount of diethyl ether to provide 3,4-dichloropicolinamide (14.8 g, 39%).

1. additionAfter the addition
2. customthe cooling bath was removed
3. temperatureto warm to room temperature over 1 h
4. stirringto stir overnight
5. customthe white solid that formed
6. filtrationwas collected through filtration
7. washwashed with water
8. extractionThe filtrate was extracted with ethyl acetate (3×300 mL)
9. customThe solid that was collected previously
10. dissolutionwas dissolved in the combined organic layers
11. washthe resulting solution was washed with brine (2×200 mL)
12. dry with materialdried over MgSO4
13. concentrationconcentrated in vacuo
14. customsonicated
15. filtrationThe remaining solid was collected through filtration
16. washwashed with minimum amount of diethyl ether

ORD 기록

ord-8301e84fc493499ca1ccebd0a2ae296c

출처 데이터셋

uspto-grants-2013_09

DOI

10.6084/m9.figshare.5104873.v1

특허 번호

US08536200B2