Triphenylphosphine → 3-(2-Bromo-ethyl)-2-chloro-4-fluoro-benzonitrile
Reaction equation
C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[Br:20]Br.[Cl:22][C:23]1[C:30]([CH2:31][CH2:32]O)=[C:29]([F:34])[CH:28]=[CH:27][C:24]=1[C:25]#[N:26]>C(Cl)Cl.CCCCCC>[Br:20][CH2:32][CH2:31][C:30]1[C:23]([Cl:22])=[C:24]([CH:27]=[CH:28][C:29]=1[F:34])[C:25]#[N:26]Participants
Conditions
- Temperature
- -10 °C
Procedure
To a 25 mL round bottomed flask equipped with a magnetic stirrer was added triphenylphosphine (1.57 g, 6 mmol) and methylene chloride (8 mL). Upon cooling the mixture to −10° C., bromine (0.28 mL, 5.5 mmol) was added dropwise. After 10 min, 2-chloro-4-fluoro-3-(2-hydroxyethyl)benzonitrile (1 g, 5 mmol) in methylene chloride (6 mL) was added and stirring was continued for 20 min while the internal reaction temperature was allowed to warm to 15° C. The mixture was then diluted with hexane (30 mL) and purified via a silica plug [hexane-Et2O (20:1) as eluent]. The combined filtrates were concentrated to furnish the title compound (1.26 g, 96%): 1H NMR (400 MHz, Acetone-d6, δ in ppm) 7.92 (dd, J=6 and 9 Hz, 1H), 7.42 (t, J=9 Hz, 1H), 3.70 (t, J=7 Hz, 2H), 3.13 (dt, J=2 and 7 Hz, 2H).
Workup
- customTo a 25 mL round bottomed flask equipped with a magnetic stirrer
- waitwas continued for 20 min while the internal reaction temperature
- temperatureto warm to 15° C
- custompurified via a silica plug [hexane-Et2O (20:1) as eluent]
- concentrationThe combined filtrates were concentrated
Sources & evidence
- ORD record
- ord-39d62f180bc34b92963b1d67aa21e31e
- Source dataset
- uspto-grants-2014_01
- Patent number
- US08629167B2
Reaction notes
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