Hydrochloric Acid → 4-(Ethoxycarbonyl)-5,6-dihydro-2H-pyran-3-carboxylic acid

Participants

Reaction Steps

A mixture of acetic anhydride (5.19 g, 4.8 mL, 50.9 mmol), DIPEA (6.58 g, 8.89 mL, 50.9 mmol) and sodium formate (5.19 g, 76.3 mmol) was stirred at RT for 1 h. A solution of ethyl 5-(trifluoromethylsulfonyloxy)-3,6-dihydro-2H-pyran-4-carboxylate (8.6 g, 25.4 mmol; prepared according to WO2010038167) in DMF (50 mL) was added dropwise, followed by the addition of palladium (II) acetate (286 mg, 1.27 mmol) and LiCl (3.24 g, 76.3 mmol). After stirring at RT for 1.5 h the black suspension was poured on 2M aqueous HCl solution (100 mL) and EtOAc (100 mL) and the layers were separated. The aqueous layer was extracted twice with EtOAc (100 mL). The organic layers were washed twice with H2O and once with brine, dried over MgSO4, filtered, treated with silica gel and evaporated. The compound was purified by silica gel chromatography on a 120 g column using an MPLC system eluting with a gradient of CH2Cl2:MeOH (100:0 to 80:20). Light brown oil (4.14 g; 81.3%). MS (ESI): m/z=199.06 [M−H]−.

Provenance & Evidence