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

HRID 1404631Notes

Reaction equation

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

Participants

Conditions

Temperature: 78 °C

Procedure

To a stirring solution of 2-(2-fluorophenyl)oxirane (5.30 g, 38.4 mmol) in toluene (65 mL) was added 4-hydroxybenzaldehyde (7.0 g, 58.0 mmol), 1M NaOH (65 mL) and PEG4000 (polyethylene glycol, 0.85 g) and the stirring mixture was heated at 78° C. overnight. The reaction 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 adsorbed onto silica gel and chromatographed, eluting with 30-40% EtOAc/hexanes to give 2 major spots. Fractions containing the higher Rf spot were combined and evaporated in vacuo to give 1.10 g (11%) of the title compound as a colorless oil. Fractions containing the lower Rf spot were combined and evaporated in vacuo to give 0.67 g (7%) of the regioisomer as a 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
customchromatographed
washeluting with 30-40% EtOAc/hexanes
customto give 2 major spots
additionFractions containing the higher Rf spot
customevaporated in vacuo

Sources & evidence

ORD record: ord-adf6b7670e95463da278f3b374d1a939
Source dataset: uspto-grants-2014_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08912335B2

Reaction notes

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