Hydrochloric Acid → 4-(3-Bromo-4-formyl-phenoxy)-3-fluoro-benzonitrile

HRID 1257074Notes

Reaction equation

[F:1][C:2]1[CH:3]=[C:4]([CH:7]=[CH:8][C:9]=1[OH:10])[C:5]#[N:6].C([O-])([O-])=O.[K+].[K+].[Br:17][C:18]1[CH:25]=[C:24](F)[CH:23]=[CH:22][C:19]=1[CH:20]=[O:21].Cl>CN(C=O)C.CCOC(C)=O>[Br:17][C:18]1[CH:25]=[C:24]([CH:23]=[CH:22][C:19]=1[CH:20]=[O:21])[O:10][C:9]1[CH:8]=[CH:7][C:4]([C:5]#[N:6])=[CH:3][C:2]=1[F:1]

Participants

Conditions

Temperature: 70 °C

Procedure

To a solution of 3-fluoro-4-hydroxy-benzonitrile (5 g, 36 mmol) in DMF (anhydrous, 100 mL) was slowly added K2CO3 (5.54 g, 40.1 mmol). After stirring for 5 minutes, to the solution was added 2-bromo-4-fluoro-benzaldehyde (8.89 g, 43.8 mmol). The reaction was heated at 70° C. and monitored by T.L.C. After 4 hours, the heating was stopped and after cooling to the room temperature, 100 mL of EtOAc was added. With stirring, 1 M HCl (˜50 mL) was slowly added until the pH was 7. The organic layer was then washed with H2O (3×50 mL), dried over MgSO4 and filtered. The filtrate was evaporated under vacuum. The residue was purified over silica gel, eluting with 12.5% EtOAc/hexanes to afford 4-(3-bromo-4-formyl-phenoxy)-3-fluoro-benzonitrile (3) 7.1 g in 61% yield. 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 10.28 (s, 1 H), 7.96 (d, J=8.60 Hz, 1 H), 7.51-7.59 (m, 2 H), 7.21-7.29 (m, 3 H), 7.03 (dd, 1 H).

Workup

waitAfter 4 hours
additionwas added
stirringWith stirring
washThe organic layer was then washed with H2O (3×50 mL)
dry with materialdried over MgSO4
filtrationfiltered
customThe filtrate was evaporated under vacuum
customThe residue was purified over silica gel
washeluting with 12.5% EtOAc/hexanes

Sources & evidence

ORD record: ord-afca214276a64184926ec4a5cb4587df
Source dataset: uspto-grants-2013_06
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08461336B2

Reaction notes

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