Tetrahydrofuran → 3-Chloro-5-[(2,6-difluoro-3-methylphenyl)oxy]benzonitrile
Reaction equation
CC([O-])(C)C.[K+].C1COCC1.[F:12][C:13]1[C:18]([CH3:19])=[CH:17][CH:16]=[C:15]([F:20])[C:14]=1[OH:21].[Cl:22][C:23]1[CH:24]=[C:25]([CH:28]=[C:29](F)[CH:30]=1)[C:26]#[N:27].C1OCCOCCOCCOCCOCCOC1>CS(C)=O.C(OCC)(=O)C.O>[Cl:22][C:23]1[CH:24]=[C:25]([CH:28]=[C:29]([O:21][C:14]2[C:15]([F:20])=[CH:16][CH:17]=[C:18]([CH3:19])[C:13]=2[F:12])[CH:30]=1)[C:26]#[N:27]Participants
Reactant 5
Product 1
Reagents, catalysts & solvents 3
Conditions
- Temperature
- 135 °C
Procedure
A 1M solution KOtBu in THF (4.41 mL, 4.41 mmol) was added to a solution of 2,6-difluoro-3-methylphenol (3 g, 20.82 mmol) in DMSO (10 mL) at 0° C. under an atmosphere of nitrogen. After 10 min, 3-chloro-5-fluorobenzonitrile (3.24 g, 20.82 mmol) and 18-CROWN-6 (0.550 g, 2.082 mmol) were added and the solution was heated to 135° C. After 6 h, the brown solution was cooled to RT and water (100 mL) and ethyl acetate (150 mL) were added. The organic layer was separated, washed with water (2×150 mL), brine (150 mL), dried over MgSO4, filtered and concentrated. The residue was purfied on silica gel (hexanes/ethyl acetate) to give the title compound (4.05 g, 70%) as a white solid (N4011-11-100). 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 7.36 (t, 1H), 7.20 (t, 1H), 7.05-7.14 (m, 2H), 6.93-7.00 (m, 1H), 2.31 (s, 3H).
Workup
- waitAfter 6 h
- temperaturethe brown solution was cooled to RT
- customThe organic layer was separated
- washwashed with water (2×150 mL), brine (150 mL)
- dry with materialdried over MgSO4
- filtrationfiltered
- concentrationconcentrated
Sources & evidence
- ORD record
- ord-ac360c0e3a224d31a7faa44b95a2ea9b
- Source dataset
- uspto-grants-2012_11
- Patent number
- US08304419B2
Reaction notes
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