Tetrahydrofuran → 5-Ethyl-3-fluoropicolinamide
Reaction equation
Br[C:2]1[CH:3]=[C:4]([F:10])[C:5]([C:8]#[N:9])=[N:6][CH:7]=1.C(=O)([O-])[O-:12].[Cs+].[Cs+].[CH2:17]1COC[CH2:18]1>C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[CH2:17]([C:2]1[CH:3]=[C:4]([F:10])[C:5]([C:8]([NH2:9])=[O:12])=[N:6][CH:7]=1)[CH3:18]Participants
Conditions
- Temperature
- 65 °C
Procedure
A mixture of 5-bromo-3-fluoropicolinonitrile (1.0 g, 5 mmol), Pd(dppf)Cl2 (82 mg, 0.1 mmol) and cesium carbonate (3.26, 10 mmol) in THF (20 mL) was degassed with N2. After addition of a solution of triethylborane (1.0 M THF, 10 mL), the mixture was heated at 65° C. for 5 h. The mixture was cooled down to room temperature, and then further cooled down in an ice bath. Into the mixture was added a solution of NaOH (1.2 g) in 20 mL of H2O, followed by H2O2 (30% aqueous 7 mL). The mixture was stirred at 0° C. for 30 min and extracted with ether (4×). The organic layer was washed with brine and dried (MgSO4), and concentrated. The product 5-ethyl-3-fluoropicolinamide (370 mg) was obtained from silica gel chromatography (elution with 0-40% EtOAc/Hex).
Workup
- customwas degassed with N2
- additionAfter addition of a solution of triethylborane (1.0 M THF, 10 mL)
- temperatureThe mixture was cooled down to room temperature
- temperaturefurther cooled down in an ice bath
- additionInto the mixture was added a solution of NaOH (1.2 g) in 20 mL of H2O
- extractionextracted with ether (4×)
- washThe organic layer was washed with brine
- dry with materialdried (MgSO4)
- concentrationconcentrated
Sources & evidence
- ORD record
- ord-5e68766c3b1b4b569851a768a6e6e842
- Source dataset
- uspto-grants-2016_08
- Patent number
- US09428475B2
Reaction notes
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