Carbon tetrabromide → 2-Bromomethyl-4'-fluorobiphenyl
Reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[CH:13]=[CH:12][CH:11]=[CH:10][C:9]=2[CH2:14]O)=[CH:4][CH:3]=1.C(Br)(Br)(Br)[Br:17].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>C(Cl)Cl>[Br:17][CH2:14][C:9]1[CH:10]=[CH:11][CH:12]=[CH:13][C:8]=1[C:5]1[CH:6]=[CH:7][C:2]([F:1])=[CH:3][CH:4]=1Participants
Reactant 3
Product 1
Reagents, catalysts & solvents 1
Conditions
- Temperature
- 0 °C
Procedure
To a solution of (4′-fluorobiphenyl-2-yl)-methanol (2.58 g, 12.8 mmol) in CH2Cl2 (100 mL), carbon tetrabromide (7.40 g, 22.3 mmol) is added. The solution is cooled to 0° C. and then triphenylphosphine (7.53 g, 28.7 mmol) is added portionwise. The reaction is stirred at 0° C. for 1.5 h and then at room temperature for 90 h before the solvent is removed. The resulting residue is partitioned between Et2O and water and then filtered. The layers are separated and the aqueous layer is extracted with Et2O. The combined organic layers are washed with water, brine and dried over Na2SO4. After concentration, the residue is purified by flash chromatography (hexane) to give 2-bromomethyl-4′-fluorobiphenyl as an oil. (an alternative preparation appears in J. Med. Chem. 2004, 47(22), 5441) 1H NMR (400 MHz, CDCl3) δ 7.53-7.50 (m, 1H), 7.43-7.31 (m, 4H), 7.24-7.21 (m, 1H), 7.15-6.80 (m, 2H), 4.42 (s, 2H).
Workup
- customat room temperature for 90 h before the solvent is removed
- customThe resulting residue is partitioned between Et2O and water
- filtrationfiltered
- customThe layers are separated
- extractionthe aqueous layer is extracted with Et2O
- washThe combined organic layers are washed with water, brine
- dry with materialdried over Na2SO4
- concentrationAfter concentration
- customthe residue is purified by flash chromatography (hexane)
Sources & evidence
- ORD record
- ord-8178bdd9481a4a4197212502d01ce149
- Source dataset
- uspto-grants-2016_03
- Patent number
- US09278969B2
Reaction notes
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