3,4-dihydro-2H-pyran → Ethyl 4-[(tetrahydro-2H-pyran-2-yloxy)methyl]-2-[4-(trifluoromethyl)phenyl]-1,3-thiazole-5-carboxylate

Participants

Reaction Steps

To a 1-L round-bottom flask equipped with a magnetic stir-bar and a N2 inlet was added Ethyl 4-(hydroxymethyl)-2-[4-(trifluoromethyl)phenyl]-1,3-thiazole-5-carboxylate (42 g, 0.127 moles, 1 eq) and dry CH2Cl2 (300 ml) at room temperature. This was followed by the addition of 3,4-dihydro-2H-pyran (14 ml, 0.152 moles, 1.2 eq) as a neat liquid and pyridinium p-toluenesulfonate (6.4 g, 25.4 mmoles, 20 mol %). The reaction mixture was stirred at room temperature overnight (10 hrs). The volatiles were then removed in vacuo and the residue was purified by flash silica gel chromatography (10% EtOAc/Hexanes to 30% EtOAc/Hexanes) to yield 34 g (64%) of pure title compound.

Provenance & Evidence