Potassium Carbonate → HCID 67257612, compound

Participants

Reaction Conditions

Reaction Steps

To a stirred mixture of methyl 4-{[(3R,4R)-3-(3-ethoxy-4-methoxyphenyl)-1,1-dioxidotetrahydro-2H-thiopyran-4-yl]carbamoyl}benzoate (22.8 g; compound C4) and K2CO3 (6.82 g) in absolute ACN (200 ml) is added POCl3 (13.6 ml) at 0° C. (ice bath). The suspension is allowed to come to RT within 1 h and is subsequently refluxed at 85° C. for 6 h. Afterwards the mixture is stirred for 12 h at RT under nitrogen atmosphere. The mixture is quenched with water (500 ml) and adjusted to pH7 by addition of 0.4 M NaOH. The ACN is destilled of and to the remaining suspension DCM (500 ml) is added. The pH value is adjusted to 8.1 by addition of aqueous sodium hydroxide solution (0.4 M) and saturated aqueous solution of sodium bicarbonate and the mixture is stirred at RT for 12 h. The organic layer is separated and the aqueous layer is extracted with DCM (300 ml). The combined organic layers are dried over sodium sulfate, filtered and evaporated in vacuo to dryness. The resulting residue is purified by flash column chromatography [silica gel, eluent system: n-hexane/EtOAc/triethylamine 11/8/1 (v/v/v)] to obtain a crude solid. The residue is treated with DIP (400 ml) and stirred at reflux temperature for 3 h. The suspension is cooled to 0° C. with an ice bath and filtered off. The filter cake is washed with DIP and dried in vacuo at 70° C. to obtain the title compound as a solid.

Provenance & Evidence