Hydrochloric Acid → 4-(3-Fluoro-5-methoxy-phenoxy)-2-methyl-benzaldehyde

HRID 1822301Notes

Reaction equation

[F:1][C:2]1[CH:3]=[C:4]([OH:10])[CH:5]=[C:6]([O:8][CH3:9])[CH:7]=1.[H-].[Na+].F[C:14]1[CH:21]=[CH:20][C:17]([CH:18]=[O:19])=[C:16]([CH3:22])[CH:15]=1.Cl>CN(C=O)C.CCOCC>[F:1][C:2]1[CH:3]=[C:4]([CH:5]=[C:6]([O:8][CH3:9])[CH:7]=1)[O:10][C:14]1[CH:21]=[CH:20][C:17]([CH:18]=[O:19])=[C:16]([CH3:22])[CH:15]=1

Participants

Conditions

Temperature: 60 °C

Procedure

A 0° C. solution of 3-fluoro-5-methoxy-phenol (2.40 g, 16.9 mmol) in dry DMF (20 mL) is treated with a 60% suspension of NaH (0.74 g, 18.5 mmol) and then stirred for 15 minutes under N2. A solution of 4-fluoro-2-methyl-benzaldehyde (2.33 g, 16.9 mmol) in DMF (10 mL) is added dropwise, and the mixture is warmed to 60° C. for 4 hours. The mixture is cooled and acidified with 1 N HCl. The mixture is then diluted with Et2O and extracted with water. The organic layer is dried (Na2SO4), and the solvent is removed in vacuo to afford crude product that is absorbed on silica gel and purified by flash chromatography using 6/1 hexanes/ethyl acetate to afford 1.40 g (32%) of the title compound. Rf=0.41 (2/1 hexanes/EtOAc). 1H NMR (400 MHz, CDCl3); MS (ES+) m/z mass calculated for C15H13O3F 260, found 261 (M+1, 100%).

Workup

temperatureThe mixture is cooled
extractionextracted with water
dry with materialThe organic layer is dried (Na2SO4)
customthe solvent is removed in vacuo
customto afford crude product that
customis absorbed on silica gel
custompurified by flash chromatography

Sources & evidence

ORD record: ord-78d155af76f74178a965eeea587052db
Source dataset: uspto-grants-2009_10
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07608639B2

Reaction notes

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