Triethyl phosphite → Diethyl 3-fluorobenzylphosphonate
Reaction equation
Br[CH2:2][C:3]1[CH:8]=[CH:7][CH:6]=[C:5]([F:9])[CH:4]=1.[CH2:10]([O:12][P:13]([O:17]CC)[O:14][CH2:15][CH3:16])[CH3:11]>>[F:9][C:5]1[CH:4]=[C:3]([CH:8]=[CH:7][CH:6]=1)[CH2:2][P:13](=[O:17])([O:14][CH2:15][CH3:16])[O:12][CH2:10][CH3:11]Participants
Conditions
- Temperature
- 150 °C
Procedure
A flask was charged with 1-(bromomethyl)-3-fluorobenzene (7.5 mL, 61.1 mmol) and treated with triethylphosphite (21.39 mL, 122 mmol) dropwise with stirring. Upon completion of the addition, the reaction was fitted with a reflux condensor (no cooling) and a slow stream of nitrogen was passed over the reaction mixture. The reaction was slowly warmed to 150° C. and held there for 2 h. The reaction was cooled to room temperature and concentrated under high vacuum to remove most of the excess triethylphosphite. The resulting residue was purified by column chromatography (50%-->100% EtOAc/Hex) to give 15.13 g (quant.) as a colorless oil. 1H-NMR (CDCl3, 500 MHz) δ 7.29 (m, 1H), 7.10 (m, 1H), 7.05 (m, 1H), 6.97 (m, 1H), 4.06 (m, 4H), 3.16 (d, J=21.7, 2H), 1.28 (t, J=7.0, 6H). 13C-NMR (CDCl3, 126 MHz) δ 162.85 (dd, J=246, 3.8), 134.2 (t, J=8.6), 130.0 (dd, J=7.7, 2.9), 125.6 (dd, J=6.7, 2.9), 116.9 (dd, J=22, 6.7, 114.0 (dd, J=21, 2.9), 62.3 (d, J=6.7), 33.7 (dd, J=138, 1.9, 16.5 (d, J=5.8).
Workup
- additionUpon completion of the addition
- customthe reaction was fitted with a reflux condensor (no cooling) and a slow stream of nitrogen
- temperatureThe reaction was cooled to room temperature
- concentrationconcentrated under high vacuum
- customto remove most of the excess triethylphosphite
- customThe resulting residue was purified by column chromatography (50%-->100% EtOAc/Hex)
- customto give 15.13 g (quant.) as a colorless oil
Sources & evidence
- ORD record
- ord-d895ae5ddc72455884a145074a10ebdd
- Source dataset
- uspto-grants-2014_04
- Patent number
- US08691821B2
Reaction notes
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