Hexamethylenetetramine → 3,5-Difluoro-4-hydroxybenzaldehyde

A stirring solution of 2,6-difluorophenol (2 g, 15.4 mmol) and hexamethylenetetramine (2.16 g, 15.4 mmol) in TFA (16 mL) was heated at reflux under argon overnight. On cooling to room temperature the solvent was evaporated in vacuum and the crude residue was taken up in DCM (35 mL). The mixture was washed with an aqueous solution of NaHCO3 (sat.) and the separated aqueous layer acidified to pH 1 with concentrated HCl. The aqueous layer was extracted with DCM (2×25 mL), the combined organic fractions dried (MgSO4) and evaporated in vacuum to afford desired product as a cream solid (1.76 g, 73%). Rf=0.39 (SiO2; cyclohexane/EtOAc (6/4); UV) 1H NMR (300 MHz; CDCl3) δ: 6.38 (br, 1H); 7.50 (d, 2H, J=6.6 Hz); 9.82 (s, 1H). 13C NMR (75 MHz; CDCl3) δ: 113.2 (dd, JCF=13.8 Hz and 7.8 Hz); 128.2 (t, JCF=6.0 Hz); 139.0 (t, JCF=16.1 Hz); 151.9 (dd, JCF=246.9 Hz and 5.3 Hz); 189.1. 19F NMR (282 MHz; CDCl3) δ: −52.2

1. temperatureat reflux under argon overnight
2. customwas evaporated in vacuum
3. washThe mixture was washed with an aqueous solution of NaHCO3 (sat.)
4. extractionThe aqueous layer was extracted with DCM (2×25 mL)
5. dry with materialthe combined organic fractions dried (MgSO4)
6. customevaporated in vacuum

ORD record

ord-52f4249fdb854768ae140f0270ba2224

Source dataset

uspto-grants-2015_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09212196B2