Reaction #43366

Reaction equation

LCAP

K2CO3

4-Chloro-2-pyridinecarboxamide

TFAA

TFAA

→

title compound

Yield 87.6%

4-Chloro-2-cyano-pyridine

Yield 87.6%

Solvents

EtOAc

Conditions

Workup

1. 1
   workup.ADDITIONThe internal temperature rose to 10° C. during the addition
2. 2
   workup.ADDITIONThe temperature at the completion of the addition
3. 3
   Otherwas 0.0° C
4. 4
   workup.ADDITIONAfter addition
5. 5
   Otherrose from 13.7 to 22.0° C
6. 6
   OtherThe mixture was transferred to a separatory funnel
7. 7
   workup.STIRRINGafter stirring for 20 min
8. 8
   OtherThe layers were separated
9. 9
   Extractionthe aqueous layer extracted with EtOAc (150 mL)
10. 10
    WashThe combined organic layers were washed with 10% aqueous citric acid (w/v, 300 mL)
11. 11
    Dryingdried (Na2SO4)
12. 12
    Filtrationfiltered
13. 13
    Concentrationconcentrated
14. 14
    DryingThe crude product was dried in a vacuum oven at 50° C. for 16 h

Procedure

4-Chloro-2-pyridinecarboxamide (93.9 g, 0.6 moles) and TEA (125 mL, 0.9 moles) in EtOAc (500 mL) was cooled to 0.2° C. via an external chiller unit. TFAA (92 mL, 0.66 moles) was added via addition funnel over 40 min. The internal temperature rose to 10° C. during the addition. The temperature at the completion of the addition was 0.0° C. After addition, the chiller was turned off. After an additional 30 min, HPLC analysis showed 4.3% (LCAP) of the starting material. An additional 8.3 mL (0.06 moles) of TFAA was added. After stirring the reaction mixture for an additional 20 min, HPLC analysis indicated complete conversion. 10% Aqueous K2CO3 (w/v, 500 mL) was added. The internal temperature rose from 13.7 to 22.0° C. The mixture was transferred to a separatory funnel after stirring for 20 min. The layers were separated and the aqueous layer extracted with EtOAc (150 mL). The combined organic layers were washed with 10% aqueous citric acid (w/v, 300 mL), dried (Na2SO4), filtered, and concentrated. The crude product was dried in a vacuum oven at 50° C. for 16 h to afford 72.85 g (87%) of the title compound: 1H NMR (400 MHz, CDCl3) δ 8.6 (m, 1 H), 7.7 (m, 1 H), 7.5 (m, 1H); 13C NMR (100 MHz, CDCl3) δ 151.8, 145.3, 134.9, 128.7, 127.4, 116.1; HPLC>99% (LCAP).

Source