Triethylamine → Ethyl 2-fluoroisonicotinate
Reaction equation
[F:1][C:2]1[CH:3]=[C:4]([CH:8]=[CH:9][N:10]=1)[C:5]([OH:7])=[O:6].[CH2:11](N(CC)CC)[CH3:12].ClC(OCC)=O>ClCCl>[F:1][C:2]1[CH:3]=[C:4]([CH:8]=[CH:9][N:10]=1)[C:5]([O:7][CH2:11][CH3:12])=[O:6]Participants
Reactant 3
Product 1
Reagents, catalysts & solvents 1
Conditions
- Temperature
- 0 °C
Procedure
To a stirred solution of 2-fluoroisonicotinic acid (27) (1.00 g, 7.09 mmol) in anhydrous dichloromethane (30 mL) was added at 0° C., under argon, triethylamine (991 μL, 7.09 mmol). After 5 min, ethyl chloroformate (681 μL, 7.09 mmol) was added and the mixture was stirred at 0° C. for 5 min before addition of N-dimethyl-4-aminopyridine (DMAP, 86 mg, 0.71 mmol). The mixture was stirred at 0° C. for 4 h. After return back to room temperature, the solvent was evaporated under vacuum and the residue was chromatographed (Al2O3, CH2Cl2) to give ester 28 (0.98 g, 5.79 mmol) as a yellow liquid. Yield 82%; Rf (Al2O3, CH2Cl2) 0.90; IR (CCl4) ν 1096, 1210, 1299, 1409, 1572, 1735 cm−1; 1H NMR (200 MHz, CDCl3) δ 1.39 (t, 3H, J=7.1 Hz), 4.40 (q, 2H, J=7.1 Hz), 7.47 (ddd, 1H, 3JH-F=2.4 Hz, J=0.8, 1.3 Hz), 7.72 (ddd, 1H, 5JH-F=1.8 Hz, J=1.3, 5.1 Hz), 8.33 (td, 1H, 4JH-F=0.8 Hz, J=0.8, 5.1 Hz).
Workup
- customAfter return back to room temperature, the solvent was evaporated under vacuum
- customthe residue was chromatographed (Al2O3, CH2Cl2)
Sources & evidence
- ORD record
- ord-0d5a504f620341ba958bd80beb86cdc7
- Source dataset
- uspto-grants-2015_09
- Patent number
- US09125937B2
Reaction notes
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