4-Hydroxybenzaldehyde → 4-(4-Formylphenoxy)benzonitrile

HRID 228191Notes

Reaction equation

F[C:2]1[CH:9]=[CH:8][C:5]([C:6]#[N:7])=[CH:4][CH:3]=1.[OH:10][C:11]1[CH:18]=[CH:17][C:14]([CH:15]=[O:16])=[CH:13][CH:12]=1.C(=O)([O-])[O-].[K+].[K+]>CC(N(C)C)=O>[CH:15]([C:14]1[CH:17]=[CH:18][C:11]([O:10][C:2]2[CH:9]=[CH:8][C:5]([C:6]#[N:7])=[CH:4][CH:3]=2)=[CH:12][CH:13]=1)=[O:16]

Participants

Conditions

Temperature: 130 °C

Procedure

Combine 4-fluorobenzonitrile (3.96 g, 32.7 mmol), 4-hydroxybenzaldehyde (3.99 g, 32.7 mmol), dimethyl acetamide (100 mL), and potassium carbonate (6.8 g, 49 mmol), stir, and heat to 130° C. After 18 h, cool to ambient temperature, partially remove the solvent in vacuo, and dilute with 100 mL of water. Extract the aqueous solution with diethyl ether (3×150 mL), wash the organic phase with water (2×100 mL), and brine (100 mL). Dry the organic phase over magnesium sulfate, filter, and concentrate under vacuum. Purify via a Biotage Flash 40L system, using a gradient: 5:95 hexanes/ethyl acetate to 50:50 hexanes/ethyl acetate to give the title compound (3.6 g, 49%) as a white solid: 1H NMR (chloroform-d): 9.95 (s, 1H), 7.92 (d, 2H), 7.68 (d, 2H), 7.14 (m, 4H).

Workup

temperaturecool to ambient temperature
custompartially remove the solvent in vacuo
additiondilute with 100 mL of water
extractionExtract the aqueous solution with diethyl ether (3×150 mL)
washwash the organic phase with water (2×100 mL), and brine (100 mL)
dry with materialDry the organic phase over magnesium sulfate
filtrationfilter
concentrationconcentrate under vacuum
customPurify via a Biotage Flash 40L system

Sources & evidence

ORD record: ord-9fee2952a494469eb276747301f17ba7
Source dataset: uspto-grants-2009_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07560463B2

Reaction notes

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