Ammonium Hydroxide → 4-Fluoro-2-methoxybenzonitrile

HRID 348159Notes

Reaction equation

Br[C:2]1[CH:7]=[CH:6][C:5]([F:8])=[CH:4][C:3]=1[O:9][CH3:10].[C:11]([Cu])#[N:12].[NH4+].[OH-]>CN1CCCC1=O>[F:8][C:5]1[CH:6]=[CH:7][C:2]([C:11]#[N:12])=[C:3]([O:9][CH3:10])[CH:4]=1

Participants

Conditions

Temperature: 180 °C

Procedure

To a solution of intermediate 126, 1-bromo-4-fluoro-2-methoxybenzene (9.0 g) in N-methylpyrrolidone (100 mL, Sure Seal; Aldrich) was added CuCN (6.6 g, 73.7 mmol, 1.8 eq.; Aldrich), and the mixture stirred at 180° C. under anhydrous nitrogen for 5.5 hrs. After cooling, 14% aqueous NH4OH (330 mL) was added and stirring continued for 45 min at room temperature. The mixture was extracted with ether (100 mL×3), and the combined extracts washed sequentially with dilute aqueous NH4OH, dilute HCl and brine, then dried (MgSO4), and concentrated to provide the title compound (5.2 g, Yield 85% in 2 steps) as a white solid: 1H NMR (CDCl3, 500 MHz) δ ppm: 3.91 (3H, s, OMe), 6.69 (1H, dd, J=2.3 Hz, J=10.5 Hz, Ar—H), 6.72 (1H, dt, J=2.5 Hz, J=J=8.0 Hz, Ar—H), 7.55 (1H, dd, J=6.5 Hz, J=8.5 Hz, Ar—H); 13C NMR (CDCl3, 125.8 Hz) δ ppm: 56.49, 98.16, 100.06, 100.27, 108.31, 108.50, 115.83 135.37, 135.46, 163.25, 163.34 165.47, 167.50. An analytical sample was obtained by trituration with ether: Anal. calcd for C8H6FNO: C, 63.57; H, 4.00; N, 9.26; found: C, 63.36; H, 3.91; N, 9.16.

Workup

temperatureAfter cooling
stirringstirring
waitcontinued for 45 min at room temperature
extractionThe mixture was extracted with ether (100 mL×3)
washthe combined extracts washed sequentially with dilute aqueous NH4OH, dilute HCl and brine
dry with materialdried (MgSO4)
concentrationconcentrated

Sources & evidence

ORD record: ord-c380f28ae60d4ca78d08cfd15f16ef8f
Source dataset: uspto-grants-2007_02
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07176196B2

Reaction notes

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