methyl 7-hydroxy-3,4-dihydro-2H-chromene-4-carboxylate

Conditions: temp:0.00; pressure:0.00; stir:

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

Procedure: Methyl 7-hydroxy-3,4-dihydro-2H-chromene-4-carboxylate (0.075 g, 0.360 mmol), N-(4-chlorophenethyl)-4-iodobenzamide (0.126 g, 0.327 mmol), 2,2,6,6-tetramethyl-3,5-heptanedione (0.00603 g, 0.0327 mmol), CuCl (0.0162 g, 0.164 mmol) and Cs2CO3 (0.213 g, 0.655 mmol) were stirred together in N-methylpyrrolidone (2 mL) at 120° C. for 3 hours. The reaction was cooled and loaded onto a silica gel samplet. The product was a eluted over using a gradient of 5% ethyl acetate/hexanes to 75% ethyl acetate/hexanes to provide the title compound (0.056 g, 37.8% yield). The reaction was cooled a eluted

Conditions: temp:130.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To 7-methoxy-3,4-dihydro-2H-chromene-4-carboxylic acid (0.71 g, 3.41 mmol) was added HBr (0.276 g, 3.41 mmol) and the reaction was heated at 130° C. for 3 hours. The reaction was cooled and concentrated, and the residue was loaded onto a silica gel samplet. The product was eluted using a gradient of 0.5% MeOH/CH2Cl2 containing 0.5% acetic acid to 10% acetic acid/CH2Cl2 containing 0.5% acetic acid. The isolated product was dissolved in MeOH (5 mL) and concentrated sulfuric acid (1 mL) was added and the reaction heated at 75° C. After 2 hours, reaction was cooled, diluted with ethyl acetate (25 mL) and washed with water (25 mL) and brine (25 mL). The organic layer was dried over magnesium sulfate and concentrated. The residue was purified by silica gel chromatography, eluting with a gradient of 0.5% MeOH/CH2Cl2 to 10% MeOH/CH2Cl2, to provide the title compound (0.312 g, 43.9% yield). The reaction was cooled concentrated The product was eluted The isolated product was dissolved in MeOH (5 mL) concentrated sulfuric acid (1 mL) was added the reaction heated at 75° C reaction was cooled washed with water (25 mL) and brine (25 mL) The organic layer was dried over magnesium sulfate concentrated The residue was purified by silica gel chromatography eluting with a gradient of 0.5% MeOH/CH2Cl2 to 10% MeOH/CH2Cl2

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

Procedure: Methyl 7-hydroxy-3,4-dihydro-2H-chromene-4-carboxylate (0.075 g, 0.360 mmol), N-(4-chlorophenethyl)-4-iodobenzamide (0.126 g, 0.327 mmol), 2,2,6,6-tetramethyl-3,5-heptanedione (0.00603 g, 0.0327 mmol), CuCl (0.0162 g, 0.164 mmol) and Cs2CO3 (0.213 g, 0.655 mmol) were stirred together in N-methylpyrrolidone (2 mL) at 120° C. for 3 hours. The reaction was cooled and loaded onto a silica gel samplet. The product was a eluted over using a gradient of 5% ethyl acetate/hexanes to 75% ethyl acetate/hexanes to provide the title compound (0.056 g, 37.8% yield). The reaction was cooled a eluted

Conditions: temp:130.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To 7-methoxy-3,4-dihydro-2H-chromene-4-carboxylic acid (0.71 g, 3.41 mmol) was added HBr (0.276 g, 3.41 mmol) and the reaction was heated at 130° C. for 3 hours. The reaction was cooled and concentrated, and the residue was loaded onto a silica gel samplet. The product was eluted using a gradient of 0.5% MeOH/CH2Cl2 containing 0.5% acetic acid to 10% acetic acid/CH2Cl2 containing 0.5% acetic acid. The isolated product was dissolved in MeOH (5 mL) and concentrated sulfuric acid (1 mL) was added and the reaction heated at 75° C. After 2 hours, reaction was cooled, diluted with ethyl acetate (25 mL) and washed with water (25 mL) and brine (25 mL). The organic layer was dried over magnesium sulfate and concentrated. The residue was purified by silica gel chromatography, eluting with a gradient of 0.5% MeOH/CH2Cl2 to 10% MeOH/CH2Cl2, to provide the title compound (0.312 g, 43.9% yield). The reaction was cooled concentrated The product was eluted The isolated product was dissolved in MeOH (5 mL) concentrated sulfuric acid (1 mL) was added the reaction heated at 75° C reaction was cooled washed with water (25 mL) and brine (25 mL) The organic layer was dried over magnesium sulfate concentrated The residue was purified by silica gel chromatography eluting with a gradient of 0.5% MeOH/CH2Cl2 to 10% MeOH/CH2Cl2

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

Procedure: Methyl 7-hydroxy-3,4-dihydro-2H-chromene-4-carboxylate (0.075 g, 0.360 mmol), N-(4-chlorophenethyl)-4-iodobenzamide (0.126 g, 0.327 mmol), 2,2,6,6-tetramethyl-3,5-heptanedione (0.00603 g, 0.0327 mmol), CuCl (0.0162 g, 0.164 mmol) and Cs2CO3 (0.213 g, 0.655 mmol) were stirred together in N-methylpyrrolidone (2 mL) at 120° C. for 3 hours. The reaction was cooled and loaded onto a silica gel samplet. The product was a eluted over using a gradient of 5% ethyl acetate/hexanes to 75% ethyl acetate/hexanes to provide the title compound (0.056 g, 37.8% yield). The reaction was cooled a eluted

Conditions: temp:130.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To 7-methoxy-3,4-dihydro-2H-chromene-4-carboxylic acid (0.71 g, 3.41 mmol) was added HBr (0.276 g, 3.41 mmol) and the reaction was heated at 130° C. for 3 hours. The reaction was cooled and concentrated, and the residue was loaded onto a silica gel samplet. The product was eluted using a gradient of 0.5% MeOH/CH2Cl2 containing 0.5% acetic acid to 10% acetic acid/CH2Cl2 containing 0.5% acetic acid. The isolated product was dissolved in MeOH (5 mL) and concentrated sulfuric acid (1 mL) was added and the reaction heated at 75° C. After 2 hours, reaction was cooled, diluted with ethyl acetate (25 mL) and washed with water (25 mL) and brine (25 mL). The organic layer was dried over magnesium sulfate and concentrated. The residue was purified by silica gel chromatography, eluting with a gradient of 0.5% MeOH/CH2Cl2 to 10% MeOH/CH2Cl2, to provide the title compound (0.312 g, 43.9% yield). The reaction was cooled concentrated The product was eluted The isolated product was dissolved in MeOH (5 mL) concentrated sulfuric acid (1 mL) was added the reaction heated at 75° C reaction was cooled washed with water (25 mL) and brine (25 mL) The organic layer was dried over magnesium sulfate concentrated The residue was purified by silica gel chromatography eluting with a gradient of 0.5% MeOH/CH2Cl2 to 10% MeOH/CH2Cl2

Conditions: temp:130.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To 7-methoxy-3,4-dihydro-2H-chromene-4-carboxylic acid (0.71 g, 3.41 mmol) was added HBr (0.276 g, 3.41 mmol) and the reaction was heated at 130° C. for 3 hours. The reaction was cooled and concentrated, and the residue was loaded onto a silica gel samplet. The product was eluted using a gradient of 0.5% MeOH/CH2Cl2 containing 0.5% acetic acid to 10% acetic acid/CH2Cl2 containing 0.5% acetic acid. The isolated product was dissolved in MeOH (5 mL) and concentrated sulfuric acid (1 mL) was added and the reaction heated at 75° C. After 2 hours, reaction was cooled, diluted with ethyl acetate (25 mL) and washed with water (25 mL) and brine (25 mL). The organic layer was dried over magnesium sulfate and concentrated. The residue was purified by silica gel chromatography, eluting with a gradient of 0.5% MeOH/CH2Cl2 to 10% MeOH/CH2Cl2, to provide the title compound (0.312 g, 43.9% yield). The reaction was cooled concentrated The product was eluted The isolated product was dissolved in MeOH (5 mL) concentrated sulfuric acid (1 mL) was added the reaction heated at 75° C reaction was cooled washed with water (25 mL) and brine (25 mL) The organic layer was dried over magnesium sulfate concentrated The residue was purified by silica gel chromatography eluting with a gradient of 0.5% MeOH/CH2Cl2 to 10% MeOH/CH2Cl2

Conditions: temp:0.00; pressure:0.00; stir:

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

Procedure: Methyl 7-hydroxy-3,4-dihydro-2H-chromene-4-carboxylate (0.075 g, 0.360 mmol), N-(4-chlorophenethyl)-4-iodobenzamide (0.126 g, 0.327 mmol), 2,2,6,6-tetramethyl-3,5-heptanedione (0.00603 g, 0.0327 mmol), CuCl (0.0162 g, 0.164 mmol) and Cs2CO3 (0.213 g, 0.655 mmol) were stirred together in N-methylpyrrolidone (2 mL) at 120° C. for 3 hours. The reaction was cooled and loaded onto a silica gel samplet. The product was a eluted over using a gradient of 5% ethyl acetate/hexanes to 75% ethyl acetate/hexanes to provide the title compound (0.056 g, 37.8% yield). The reaction was cooled a eluted

Conditions: temp:130.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To 7-methoxy-3,4-dihydro-2H-chromene-4-carboxylic acid (0.71 g, 3.41 mmol) was added HBr (0.276 g, 3.41 mmol) and the reaction was heated at 130° C. for 3 hours. The reaction was cooled and concentrated, and the residue was loaded onto a silica gel samplet. The product was eluted using a gradient of 0.5% MeOH/CH2Cl2 containing 0.5% acetic acid to 10% acetic acid/CH2Cl2 containing 0.5% acetic acid. The isolated product was dissolved in MeOH (5 mL) and concentrated sulfuric acid (1 mL) was added and the reaction heated at 75° C. After 2 hours, reaction was cooled, diluted with ethyl acetate (25 mL) and washed with water (25 mL) and brine (25 mL). The organic layer was dried over magnesium sulfate and concentrated. The residue was purified by silica gel chromatography, eluting with a gradient of 0.5% MeOH/CH2Cl2 to 10% MeOH/CH2Cl2, to provide the title compound (0.312 g, 43.9% yield). The reaction was cooled concentrated The product was eluted The isolated product was dissolved in MeOH (5 mL) concentrated sulfuric acid (1 mL) was added the reaction heated at 75° C reaction was cooled washed with water (25 mL) and brine (25 mL) The organic layer was dried over magnesium sulfate concentrated The residue was purified by silica gel chromatography eluting with a gradient of 0.5% MeOH/CH2Cl2 to 10% MeOH/CH2Cl2

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

Procedure: Methyl 7-hydroxy-3,4-dihydro-2H-chromene-4-carboxylate (0.075 g, 0.360 mmol), N-(4-chlorophenethyl)-4-iodobenzamide (0.126 g, 0.327 mmol), 2,2,6,6-tetramethyl-3,5-heptanedione (0.00603 g, 0.0327 mmol), CuCl (0.0162 g, 0.164 mmol) and Cs2CO3 (0.213 g, 0.655 mmol) were stirred together in N-methylpyrrolidone (2 mL) at 120° C. for 3 hours. The reaction was cooled and loaded onto a silica gel samplet. The product was a eluted over using a gradient of 5% ethyl acetate/hexanes to 75% ethyl acetate/hexanes to provide the title compound (0.056 g, 37.8% yield). The reaction was cooled a eluted