Dimethylformamide → 2-Fluoro-3-(hydroxymethyl)pyridine
Reaction equation
S(Cl)(Cl)=O.[F:5][C:6]1[N:14]=[CH:13][CH:12]=[CH:11][C:7]=1[C:8](O)=[O:9].CN(C)C=O.[BH4-].[Na+]>C1C=CC=CC=1.O1CCOCC1.C([O-])(O)=O.[Na+]>[F:5][C:6]1[C:7]([CH2:8][OH:9])=[CH:11][CH:12]=[CH:13][N:14]=1Participants
Procedure
Thionyl chloride (0.43 mL, 5.87 mmol) was added to a slurry of 2-fluoronicotinic acid (9, 0.69 g, 4.89 mmol) and N,N-dimethylformamide (0.1 mL, catalytic amount) in benzene (60 mL) at room temperature under nitrogen, after which the mixture was heated at reflux for 3 h. The solvent was removed under reduced pressure to provide an amber oil that was dissolved in 1,4-dioxane (40 mL) under nitrogen. The solution was treated with sodium borohydride (0.38 g, 10.0 mmol) and the mixture was stirred at room temperature for 24 h. The suspension was diluted with saturated NaHCO3 solution (200 mL) and extracted with diethyl ether (3×200 mL). The combined organic extracts were dried over Na2SO4, filtered and the solvents were removed under reduced pressure to provide the title compound: 1H NMR (300 MHz) 8.13 (d, J=3.7 Hz, 1H), 7.93-7.88 (m, 1H), 7.24-7.19 (m, 1H), 4.78 (s, 2H), 2.14 (bs, 1H) ppm.
Workup
- temperatureafter which the mixture was heated
- temperatureat reflux for 3 h
- customThe solvent was removed under reduced pressure
- customto provide an amber oil that
- extractionextracted with diethyl ether (3×200 mL)
- dry with materialThe combined organic extracts were dried over Na2SO4
- filtrationfiltered
- customthe solvents were removed under reduced pressure
Sources & evidence
- ORD record
- ord-ec8a6df2ffe64e73bac8c7c93c5e6331
- Source dataset
- uspto-grants-2004_10
- Patent number
- US06800651B2
Reaction notes
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