6-methoxy-1-benzofuran-2-carbonitrile

Conditions: temp:100.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Potassium carbonate (15.1 g) and molecular sieves 4A (3 g) were added to a DMF solution (100 ml) of (2-formyl-5-methoxyphenyl)oxyacetonitrile (10.4 g), which was stirred at 100° C. for 10 hours. Water was added to the reaction mixture, which was extracted with ethyl acetate. The organic layer was washed with water and a saturated aqueous sodium chloride solution, then dried and concentrated. The residue was purified by silica gel column chromatography (ethyl acetate) to obtain the entitled compound (4.65 g). was extracted with ethyl acetate The organic layer was washed with water a saturated aqueous sodium chloride solution, then dried concentrated The residue was purified by silica gel column chromatography (ethyl acetate)

Conditions: temp:50.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution (20 mL) of 6-methoxy-1-benzofuran-2-carbonitrile (1.00 g) synthesized above in tetrahydrofuran was added 1.0M cyclohexylmagnesium bromide tetrahydrofuran solution (11.5 mL), and the mixture was stirred at 50° C. overnight, and stirred with heating under reflux for 1 hr. Saturated aqueous ammonium chloride solution was added to quench the reaction, and the mixture was extracted with ethyl acetate. The extract was washed with saturated brine, dried over magnesium sulfate, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (ethyl acetate:hexane=1:9, volume ratio) to give the title object compound (584 mg, 39%) as a yellow solid. stirred with heating under reflux for 1 hr to quench the reaction the mixture was extracted with ethyl acetate The extract was washed with saturated brine dried over magnesium sulfate concentrated under reduced pressure The residue was purified by silica gel column chromatography (ethyl acetate:hexane=1:9, volume ratio)

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a mixture of 2-hydroxy-4-methoxybenzaldehyde (10.0 g), bromoacetonitrile (5.04 mL) and acetone (100 mL) was added potassium carbonate (18.1 g), and the mixture was stirred at room temperature for 3 hr. The insoluble material was filtered off, and the filtrate was concentrated under reduced pressure to give a pale-brown solid. To a solution (100 mL) of the obtained solid in N,N-dimethylformamide was added 1,8-diazabicyclo[5.4.0]undec-7-ene (9.83 mL), and the mixture was stirred at 140° C. for 1.5 hr. The reaction mixture was concentrated under reduced pressure, 1N hydrochloric acid was added, and the mixture was extracted with ethyl acetate. The extract was washed with saturated brine, dried over magnesium sulfate, and concentrated under reduced pressure. Ethyl acetate was added to the residue, the insoluble material was filtered off, and the filtrate was concentrated under reduced pressure. The residue was purified by silica gel column chromatography (ethyl acetate:hexane=3:17, volume ratio) to give the title object compound (5.32 g, 47%) as a yellow solid. The insoluble material was filtered off the filtrate was concentrated under reduced pressure to give a pale-brown solid the mixture was stirred at 140° C. for 1.5 hr The reaction mixture was concentrated under reduced pressure, 1N hydrochloric acid was added the mixture was extracted with ethyl acetate The extract was washed with saturated brine dried over magnesium sulfate concentrated under reduced pressure Ethyl acetate was added to the residue the insoluble material was filtered off the filtrate was concentrated under reduced pressure The residue was purified by silica gel column chromatography (ethyl acetate:hexane=3:17, volume ratio)