1-Bromo-2-fluoro-4-(methoxymethyl)benzene

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

Procedure: Following the general method as outlined in Intermediate 20, starting from (4-chloro-2-ethynyl-phenoxy)-acetic acid tert-butyl ester (Intermediate 3) and 1-bromo-2-fluoro-4-(methoxymethyl)benzene (obtained in Step 1), the title compound was obtained as a dark orange sticky solid after purification by flash column chromatography (silica), eluting with cyclohexane containing increasing amounts of EtOAc.

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

Procedure: A solution of 4-bromo-3-fluorobenzyl methanesulfonate (Intermediate 18, 286 mg; 1.01 mmol) and 2,6-lutidine (234 μL; 2.0 mmol) in methanol (4 mL) was stirred for 16 hours at RT. Additional aliquots of 2,6-lutidine (234 μL; 2.0 mmol each) were added once a day for a total of three days, during which stirring was continued at RT. The mixture was taken up in Et2O, washed with water, HCl (0.1N in water) and brine. The organic phase was dried over MgSO4, filtered and concentrated with moderate vacuum and without heating affording the title compound in a mixture with ethyl ether. was continued at RT washed with water, HCl (0.1N in water) and brine The organic phase was dried over MgSO4 filtered concentrated with moderate vacuum without heating

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

Procedure: A solution of 4-bromo-3-fluorobenzyl methanesulfonate (Intermediate 18, 286 mg; 1.01 mmol) and 2,6-lutidine (234 μL; 2.0 mmol) in methanol (4 mL) was stirred for 16 hours at RT. Additional aliquots of 2,6-lutidine (234 μL; 2.0 mmol each) were added once a day for a total of three days, during which stirring was continued at RT. The mixture was taken up in Et2O, washed with water, HCl (0.1N in water) and brine. The organic phase was dried over MgSO4, filtered and concentrated with moderate vacuum and without heating affording the title compound in a mixture with ethyl ether. was continued at RT washed with water, HCl (0.1N in water) and brine The organic phase was dried over MgSO4 filtered concentrated with moderate vacuum without heating