Hydrochloric Acid → HCID 11631837, compound

Participants

Reaction Conditions

Reaction Steps

To a 5-liter, 4-neck flask equipped with a mechanical stirrer, a condenser fitted with nitrogen inlet, a cooling bath and thermal couple were added 882 g anhydrous THF and 250 g (1.05 mol) 2-cyano-3-naphthalen-1-yl-acrylic acid methyl ester 1. The mixture was cooled to 5° C. and 1098 g (1.09 mol) of a 1 M THF solution of 2-methoxyphenylmagnesium bromide 2 was slowly charged into the reaction mixture through an addition funnel while maintaining the temperature at 0-10° C. The mixture was stirred for an additional 30 min. Methyl iodide (598 g, 4.21 mol) then was added in one portion. The mixture was stirred at 40° C. for 28 hours and then cooled to 25° C. The mixture was treated with 943 g of 0.5 N HCl and the lower aqueous phase was separated and retained. The organic layer was concentrated by distillation until 871 g distillate was collected. The organic concentrate then was cooled to 35° C. and the aqueous layer was combined with the organic. To the mixture then was added 506 g methanol. The mixture was cooled to 0° C. and the product was filtered. The wet cake was washed with a mixture of 333 g of methanol and 666 g of water. The product 3 was dried in an oven at 55° C. under vacuum. Yield: 306 g, 81%. The diastereomeric excess was typically 100%.

Provenance & Evidence