4-Fluorobenzonitrile → HCID 57424996, compound
Reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([OH:8])=[CH:4][C:3]=1[CH3:9].F[C:11]1[CH:18]=[CH:17][C:14]([C:15]#[N:16])=[CH:13][CH:12]=1>>[F:1][C:2]1[CH:7]=[CH:6][C:5]([O:8][C:11]2[CH:18]=[CH:17][C:14]([C:15]#[N:16])=[CH:13][CH:12]=2)=[CH:4][C:3]=1[CH3:9]Participants
Procedure
4-Fluoro-3-methylphenol and 4-fluorobenzonitrile were coupled following the procedure outlined in example 28 to give 4-(4-fluoro-3-methylphenoxy)benzonitrile. A mixture of 4-(4-fluoro-3-methylphenoxy)benzonitrile (1.1 g, 4.8 mmol), N-bromosuccinimide (NBS, 1.0 g, 5.6 mmol), dibenzoyl peroxide (90 mg, 0.37 mmol), and CCl4 (20 mL) was heated at reflux under N2. After 1 h, a second aliquot of dibenzoyl peroxide was added. After an additional 3 h, a second aliquot of NBS and a third aliquot of dibenzoyl peroxide were added. After an additional 4 h, a fourth aliquot of dibenzoyl peroxide was added. After an additional 15 h, the reaction was allowed to cool to rt and purified by silica gel chromatography (hexanes:ethyl acetate—1:0→4:1) to give an off-white solid. MS (ESI): 306/308 (M+H). A similar reaction sequence as outlined in example 1 was followed using the above bromide and 1-(2,2-dimethylpropyl)-4-propyl-1H-indol-5-ol. 1H NMR (500 MHz, DMSO) δ 8.01 (d, 2H), 7.33 (t, 1H), 7.30-7.24 (m, 2H), 7.21 (d, 1H), 7.21-7.13 (m, 3H), 6.98 (d, 1H), 6.37 (d, 1H), 5.12 (s, 2H), 3.90 (s, 2H), 2.71 (t, 2H), 1.53-1.43 (m, 2H), 0.91 (s, 9H), 0.78 (t, 3H). MS (ESI): 514.2 (M+H).
Sources & evidence
- ORD record
- ord-d528859d4be34f57927ee1e83cda8089
- Source dataset
- uspto-grants-2011_06
- Patent number
- US07960417B2
Reaction notes
Loading…