5-bromo-2-methoxy-3-(1-methylcyclopropyl)benzaldehyde

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

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

Conditions: temp:60.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: step 3—To a solution of 130 (0.44 g, 1.7 mmol) in DMF (4 mL) was added K2CO3 (0.60 g, 4.4 mmol) and iodomethane (0.32 g, 2.3 mmol). The resulting mixture was stirred at 60° C. for 2 h. The reaction mixture was cooled to RT and partitioned between water and Et2O. The organic layer was washed sequentially with water and brine, dried (Na2SO4), filtered and concentrated to afford 0.47 g (96%) of 5-bromo-2-methoxy-3-(1-methylcyclopropyl)benzaldehyde (132) as a light yellow solid. The reaction mixture was cooled to RT partitioned between water and Et2O The organic layer was washed sequentially with water and brine dried (Na2SO4) filtered concentrated

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

Procedure: Sodium hydride (60% dispersion, 0.10 g, 2.6 mmol) and 15-crown-5 (0.038 g, 0.17 mmol) were added to THF (5 mL) at 0° C. and stirred for 5 min. To the reaction mixture was then added dropwise over 5 min a solution of diethyl (4-nitrobenzyl)phosphonate (0.52 g, 1.9 mmol) in THF (5 mL), and stirring was continued at 0° C. for 5 min. To this reaction mixture was then added dropwise over 10 min a solution of 74b (0.47 g, 1.7 mmol) in THF (10 mL). The reaction mixture was stirred for 30 min at 0° C. then for 90 min at RT. Water was carefully added, and the mixture was partitioned between water and EtOAc. The EtOAc layer was washed sequentially with water and brine, dried (Na2SO4), filtered and concentrated. The crude residue was purified by SiO2 chromatography eluting with EtOAc/hexane to afford 0.67 g (94%) of 5-bromo-2-methoxy-1-(1-methylcyclopropyl)-3-[(E)-2-(4-nitrophenyl)vinyl]benzene (75) as a yellow solid (0.67 g, 94%). stirring was continued at 0° C. for 5 min The reaction mixture was stirred for 30 min at 0° C. for 90 min at RT the mixture was partitioned between water and EtOAc The EtOAc layer was washed sequentially with water and brine dried (Na2SO4) filtered concentrated The crude residue was purified by SiO2 chromatography eluting with EtOAc/hexane

Conditions: temp:60.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: step 3—To a solution of 74a (0.44 g, 1.7 mmol) in DMF (4 mL) was added K2CO3 (0.60 g, 4.4 mmol) and iodomethane (0.32 g, 2.3 mmol). The resulting mixture was stirred at 60° C. for 2 h. The reaction mixture was cooled to RT and partitioned between water and Et2O. The organic layer was washed sequentially with water and brine, dried (Na2SO4), filtered and concentrated to afford 0.47 g (96%) of 5-bromo-2-methoxy-3-(1-methylcyclopropyl)benzaldehyde (74b) as a light yellow solid. The reaction mixture was cooled to RT partitioned between water and Et2O The organic layer was washed sequentially with water and brine dried (Na2SO4) filtered concentrated