4-Hydroxybenzaldehyde → 4-[2-(3-Fluorophenyl)-2-hydroxyethoxy]benzaldehyde

HRID 562940Notes

Reaction equation

[F:1][C:2]1[CH:3]=[C:4]([CH:8]2[CH2:10][O:9]2)[CH:5]=[CH:6][CH:7]=1.[OH:11][C:12]1[CH:19]=[CH:18][C:15]([CH:16]=[O:17])=[CH:14][CH:13]=1.[OH-].[Na+]>C1(C)C=CC=CC=1>[F:1][C:2]1[CH:3]=[C:4]([CH:8]([OH:9])[CH2:10][O:11][C:12]2[CH:19]=[CH:18][C:15]([CH:16]=[O:17])=[CH:14][CH:13]=2)[CH:5]=[CH:6][CH:7]=1

Participants

Conditions

Temperature: 78 °C

Procedure

To a stirring solution of 2-(3-fluorophenyl)oxirane (5.60 g, 40.5 mmol) in toluene (65 ml) was added 4-hydroxybenzaldehyde (7.40 g, 61.0 mmol), 1M NaOH (65 ml) and PEG4000 (polyethylene glycol, 0.85 g) and the stirring mixture was heated at 78° C. overnight. The reaction mixture was allowed to cool to RT and then extracted with EtOAc (2×150 ml). The combined extracts were washed with brine, dried (Na2SO4), filtered and evaporated in vacuo. The resulting light brown oil was chromatographed eluting with 30-40% EtOAc/hexanes. There are 2 major spots. Fractions containing the higher Rf spot were combined and evaporated in vacuo to give 1.78 g (17%) of the title compound as a white solid. Fractions containing the lower Rf spot were combined and evaporated in vacuo to give 0.90 g (9%) of the regioisomer as a nearly colorless oil.

Workup

temperatureto cool to RT
extractionextracted with EtOAc (2×150 ml)
washThe combined extracts were washed with brine
dry with materialdried (Na2SO4)
filtrationfiltered
customevaporated in vacuo
customThe resulting light brown oil was chromatographed
washeluting with 30-40% EtOAc/hexanes
additionFractions containing the higher Rf spot
customevaporated in vacuo

Sources & evidence

ORD record: ord-3b149354eea44da0995dd3054c91d64a
Source dataset: uspto-grants-2011_11
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08067450B2

Reaction notes

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