Pyridine → 2-formyl-3-methyl-5-(tetrahydro-2H-pyran-2-yloxy)phenyl trifluoromethanesulfonate

HRID 1798032Notes

Reaction equation

[OH:1][C:2]1[CH:9]=[C:8]([O:10][CH:11]2[CH2:16][CH2:15][CH2:14][CH2:13][O:12]2)[CH:7]=[C:6]([CH3:17])[C:3]=1[CH:4]=[O:5].N1C=CC=CC=1.[O:24](S(C(F)(F)F)(=O)=O)[S:25]([C:28]([F:31])([F:30])[F:29])(=O)=[O:26]>ClCCl.[Cl-].[Na+].O>[CH:4]([C:3]1[C:6]([CH3:17])=[CH:7][C:8]([O:10][CH:11]2[CH2:16][CH2:15][CH2:14][CH2:13][O:12]2)=[CH:9][C:2]=1[O:1][S:25]([C:28]([F:31])([F:30])[F:29])(=[O:26])=[O:24])=[O:5]

Participants

Conditions

Temperature: 0 °C

Procedure

To a solution of 2-hydroxy-6-methyl-4-(tetrahydro-pyran-2-yloxy)-benzaldehyde (8.70 g, 36.8 mmol) and pyridine (14.56 g, 184.1 mmol) in dichloromethane (40 mL) was slowly added Tf2O (15.58 g, 55.2 mol) at −10 to 0° C. The mixture was stirred at 0° C. for 3 hours. The mixture was diluted with cold brine and extracted with 50% EtOAc/hexane. The organic extracts were washed with brine, dried and concentrated in vacuo. The residue was purified by silica gel flash column chromatography (EtOAc/hexane=1:4) to give pure product (9.48 g, 69.3%). 1H NMR (400 MHz, CDCl3) δ ppm 10.35 (s, 1H), 6.86-7.03 (m, 2H), 5.53 (t, J=2.93 Hz, 1H), 3.79 (m, 1 H), 3.55-3.71 (m, 1H), 2.65 (s, 3H), 1.84-2.05 (m, 3 H), 1.51-1.78 (m, 3 H). MS (ESI) m/z=369 [M+H]+.

Workup

customat −10 to 0° C
extractionextracted with 50% EtOAc/hexane
washThe organic extracts were washed with brine
customdried
concentrationconcentrated in vacuo
customThe residue was purified by silica gel flash column chromatography (EtOAc/hexane=1:4)

Sources & evidence

ORD record: ord-1956f76629274526bf70bb455876d63b
Source dataset: uspto-grants-2013_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08343944B2

Reaction notes

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