methyl 4-(cyanomethyl)-3-fluorobenzoate

Conditions: temp:75.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of methyl 4-(cyanomethyl)-3-fluorobenzoate (8 g, 41 mmol) and resorcinol (6.8 g, 62 mmol) in BF3-Et2O (100 ml) was bubbled with HCl at 0° C. for 15 min. The mixture was stirred at 75° C. for 16 hours. Then H2O (100 ml) was added and the solution was heated at 95° C. for 16 hours. The mixture was cooled to room temperature and neutralized by Na2CO3 and extracted with EtOAc (100 ml×3). The organic layers were combined, dried with anhydrous Na2SO4, filtered and evaporated to give the crude product. Purification by column chromatography (PE/EtOAc=10/1 to 3/1) gave Intermediate I as a white solid (6 g, 48%). the solution was heated at 95° C. for 16 hours The mixture was cooled to room temperature extracted with EtOAc (100 ml×3) dried with anhydrous Na2SO4 filtered evaporated to give the crude product Purification by column chromatography (PE/EtOAc=10/1 to 3/1)

Conditions: temp:65.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of methyl 4-(bromomethyl)-3-fluorobenzoate (18 g, 73 mmol) in MeOH (150 ml) was added the solution of NaCN (7.2 g, 146 mmol) in H2O (40 ml). The mixture was stirred at 65° C. for 5 hours. Most of MeOH was evaporated and additional water was added and extracted by EtOAc (200 ml×3), dried with anhydrous Na2SO4, filtered and evaporated to give the crude product. Purification by column chromatography (PE/EtOAc=50/1 to 10/1) gave the product (8 g, 63.8%). Most of MeOH was evaporated additional water was added extracted by EtOAc (200 ml×3) dried with anhydrous Na2SO4 filtered evaporated to give the crude product Purification by column chromatography (PE/EtOAc=50/1 to 10/1)

Conditions: temp:75.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of methyl 4-(cyanomethyl)-3-fluorobenzoate (8 g, 41 mmol) and resorcinol (6.8 g, 62 mmol) in BF3-Et2O (100 ml) was bubbled with HCl at 0° C. for 15 min. The mixture was stirred at 75° C. for 16 hours. Then H2O (100 ml) was added and the solution was heated at 95° C. for 16 hours. The mixture was cooled to room temperature and neutralized by Na2CO3 and extracted with EtOAc (100 ml×3). The organic layers were combined, dried with anhydrous Na2SO4, filtered and evaporated to give the crude product. Purification by column chromatography (PE/EtOAc=10/1 to 3/1) gave Intermediate I as a white solid (6 g, 48%). the solution was heated at 95° C. for 16 hours The mixture was cooled to room temperature extracted with EtOAc (100 ml×3) dried with anhydrous Na2SO4 filtered evaporated to give the crude product Purification by column chromatography (PE/EtOAc=10/1 to 3/1)

Conditions: temp:65.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of methyl 4-(bromomethyl)-3-fluorobenzoate (18 g, 73 mmol) in MeOH (150 ml) was added the solution of NaCN (7.2 g, 146 mmol) in H2O (40 ml). The mixture was stirred at 65° C. for 5 hours. Most of MeOH was evaporated and additional water was added and extracted by EtOAc (200 ml×3), dried with anhydrous Na2SO4, filtered and evaporated to give the crude product. Purification by column chromatography (PE/EtOAc=50/1 to 10/1) gave the product (8 g, 63.8%). Most of MeOH was evaporated additional water was added extracted by EtOAc (200 ml×3) dried with anhydrous Na2SO4 filtered evaporated to give the crude product Purification by column chromatography (PE/EtOAc=50/1 to 10/1)

Conditions: temp:75.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of methyl 4-(cyanomethyl)-3-fluorobenzoate (8 g, 41 mmol) and resorcinol (6.8 g, 62 mmol) in BF3-Et2O (100 ml) was bubbled with HCl at 0° C. for 15 min. The mixture was stirred at 75° C. for 16 hours. Then H2O (100 ml) was added and the solution was heated at 95° C. for 16 hours. The mixture was cooled to room temperature and neutralized by Na2CO3 and extracted with EtOAc (100 ml×3). The organic layers were combined, dried with anhydrous Na2SO4, filtered and evaporated to give the crude product. Purification by column chromatography (PE/EtOAc=10/1 to 3/1) gave Intermediate I as a white solid (6 g, 48%). the solution was heated at 95° C. for 16 hours The mixture was cooled to room temperature extracted with EtOAc (100 ml×3) dried with anhydrous Na2SO4 filtered evaporated to give the crude product Purification by column chromatography (PE/EtOAc=10/1 to 3/1)

Conditions: temp:65.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of methyl 4-(bromomethyl)-3-fluorobenzoate (18 g, 73 mmol) in MeOH (150 ml) was added the solution of NaCN (7.2 g, 146 mmol) in H2O (40 ml). The mixture was stirred at 65° C. for 5 hours. Most of MeOH was evaporated and additional water was added and extracted by EtOAc (200 ml×3), dried with anhydrous Na2SO4, filtered and evaporated to give the crude product. Purification by column chromatography (PE/EtOAc=50/1 to 10/1) gave the product (8 g, 63.8%). Most of MeOH was evaporated additional water was added extracted by EtOAc (200 ml×3) dried with anhydrous Na2SO4 filtered evaporated to give the crude product Purification by column chromatography (PE/EtOAc=50/1 to 10/1)

Conditions: temp:75.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of methyl 4-(cyanomethyl)-3-fluorobenzoate (8 g, 41 mmol) and resorcinol (6.8 g, 62 mmol) in BF3-Et2O (100 ml) was bubbled with HCl at 0° C. for 15 min. The mixture was stirred at 75° C. for 16 hours. Then H2O (100 ml) was added and the solution was heated at 95° C. for 16 hours. The mixture was cooled to room temperature and neutralized by Na2CO3 and extracted with EtOAc (100 ml×3). The organic layers were combined, dried with anhydrous Na2SO4, filtered and evaporated to give the crude product. Purification by column chromatography (PE/EtOAc=10/1 to 3/1) gave Intermediate I as a white solid (6 g, 48%). the solution was heated at 95° C. for 16 hours The mixture was cooled to room temperature extracted with EtOAc (100 ml×3) dried with anhydrous Na2SO4 filtered evaporated to give the crude product Purification by column chromatography (PE/EtOAc=10/1 to 3/1)

Conditions: temp:65.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of methyl 4-(bromomethyl)-3-fluorobenzoate (18 g, 73 mmol) in MeOH (150 ml) was added the solution of NaCN (7.2 g, 146 mmol) in H2O (40 ml). The mixture was stirred at 65° C. for 5 hours. Most of MeOH was evaporated and additional water was added and extracted by EtOAc (200 ml×3), dried with anhydrous Na2SO4, filtered and evaporated to give the crude product. Purification by column chromatography (PE/EtOAc=50/1 to 10/1) gave the product (8 g, 63.8%). Most of MeOH was evaporated additional water was added extracted by EtOAc (200 ml×3) dried with anhydrous Na2SO4 filtered evaporated to give the crude product Purification by column chromatography (PE/EtOAc=50/1 to 10/1)

Conditions: temp:75.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of methyl 4-(cyanomethyl)-3-fluorobenzoate (8 g, 41 mmol) and resorcinol (6.8 g, 62 mmol) in BF3-Et2O (100 ml) was bubbled with HCl at 0° C. for 15 min. The mixture was stirred at 75° C. for 16 hours. Then H2O (100 ml) was added and the solution was heated at 95° C. for 16 hours. The mixture was cooled to room temperature and neutralized by Na2CO3 and extracted with EtOAc (100 ml×3). The organic layers were combined, dried with anhydrous Na2SO4, filtered and evaporated to give the crude product. Purification by column chromatography (PE/EtOAc=10/1 to 3/1) gave Intermediate I as a white solid (6 g, 48%). the solution was heated at 95° C. for 16 hours The mixture was cooled to room temperature extracted with EtOAc (100 ml×3) dried with anhydrous Na2SO4 filtered evaporated to give the crude product Purification by column chromatography (PE/EtOAc=10/1 to 3/1)

Conditions: temp:65.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of methyl 4-(bromomethyl)-3-fluorobenzoate (18 g, 73 mmol) in MeOH (150 ml) was added the solution of NaCN (7.2 g, 146 mmol) in H2O (40 ml). The mixture was stirred at 65° C. for 5 hours. Most of MeOH was evaporated and additional water was added and extracted by EtOAc (200 ml×3), dried with anhydrous Na2SO4, filtered and evaporated to give the crude product. Purification by column chromatography (PE/EtOAc=50/1 to 10/1) gave the product (8 g, 63.8%). Most of MeOH was evaporated additional water was added extracted by EtOAc (200 ml×3) dried with anhydrous Na2SO4 filtered evaporated to give the crude product Purification by column chromatography (PE/EtOAc=50/1 to 10/1)