2-bromo-5-propan-2-yloxybenzaldehyde

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a suspension of 1.85 g (77.1 mmol) NaH in 130 mL dry THF, 25.4 g (75.1 mmol) tert-butoxycarbonyl-1-ethoxycarbonylethylidendiethoxy-phosphorane (2) was added dropwise at 0° C., The reaction mixture was stirred for 6 h at 0° C. under Ar. This solution was added under Ar dropwise at 0° C. to 15.5 g (63.5 mmol) 2-bromo-5-isopropoxy-benzaldehyde (1), dissolved in 80 mL dry THF. The cooling bath was removed and the reaction mixture was stirred overnight at room temperature. 20 mL water was added and the solvent was removed under reduced pressure. The residue was partitioned between water and dichloromethane. The organic layers were dried (MgSo4), filtered and the solvent was removed under reduced pressure to afford 16.5 g (61%) (E)-3-carboethoxy-4-(2'-bromo-5-isopropylphenyl)-3-butenic acid-tert-butyl ester as a yellow oil. was added dropwise at 0° C. The cooling bath was removed the reaction mixture was stirred overnight at room temperature 20 mL water was added the solvent was removed under reduced pressure The residue was partitioned between water and dichloromethane The organic layers were dried (MgSo4) filtered the solvent was removed under reduced pressure

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a suspension of 1.85 g (77.1 mmol) NaH in 130 mL dry THF, 25.4 g (75.1 mmol) tert-butoxycarbonyl-1-ethoxycarbonylethylidendiethoxy-phosphorane (2) was added dropwise at 0° C., The reaction mixture was stirred for 6 h at 0° C. under Ar. This solution was added under Ar dropwise at 0° C. to 15.5 g (63.5 mmol) 2-bromo-5-isopropoxy-benzaldehyde (1), dissolved in 80 mL dry THF. The cooling bath was removed and the reaction mixture was stirred overnight at room temperature. 20 mL water was added and the solvent was removed under reduced pressure. The residue was partitioned between water and dichloromethane. The organic layers were dried (MgSo4), filtered and the solvent was removed under reduced pressure to afford 16.5 g (61%) (E)-3-carboethoxy-4-(2'-bromo-5-isopropylphenyl)-3-butenic acid-tert-butyl ester as a yellow oil. was added dropwise at 0° C. The cooling bath was removed the reaction mixture was stirred overnight at room temperature 20 mL water was added the solvent was removed under reduced pressure The residue was partitioned between water and dichloromethane The organic layers were dried (MgSo4) filtered the solvent was removed under reduced pressure

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

Procedure: To a suspension of 50.0 g (110 mmol) 3-hydroxybenzaldehyde and 100 g (725 mmol) dry K2CO3 in 100 mL dry DMF, 61.5 g (500 mmol) isopropylbromide was added at room temperature. The reaction mixture was heated for 17 h at 90° C. The solvent was removed under reduced pressure and the residue was partitioned between 2N NaOH and toluene. The collected organic layers were dried (MgSO4), filtered and the solvent removed under pressure. The residue was distilled in vacuo to give 58.8 g (88%) colorless liquid. To a solution of 57.0 g (347 mmol) 3-isopropoxybenzaldehyde in 200 mL dichloromethane 30.5 g (372 mmol) NaOAc was added. After that a solution of 55.5 g (347 mmol) bromine in 50 mL dichloromethane was added dropwise and the reaction mixture was stirred overnight. The reaction mixture was extracted with saturated aqueous Na2SO3 and the combined organic phases were dried (MgSO4), filtered and concentrated under reduced pressure. The residue was distilled in vacuo to give 1 (52.1 g, 62%) as a yellow oil. The reaction mixture was extracted with saturated aqueous Na2SO3 the combined organic phases were dried (MgSO4) filtered concentrated under reduced pressure The residue was distilled in vacuo

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a suspension of 1.85 g (77.1 mmol) NaH in 130 mL dry THF, 25.4 g (75.1 mmol) tert-butoxycarbonyl-1-ethoxycarbonylethylidendiethoxy-phosphorane (2) was added dropwise at 0° C., The reaction mixture was stirred for 6 h at 0° C. under Ar. This solution was added under Ar dropwise at 0° C. to 15.5 g (63.5 mmol) 2-bromo-5-isopropoxy-benzaldehyde (1), dissolved in 80 mL dry THF. The cooling bath was removed and the reaction mixture was stirred overnight at room temperature. 20 mL water was added and the solvent was removed under reduced pressure. The residue was partitioned between water and dichloromethane. The organic layers were dried (MgSO4), filtered and the solvent was removed under reduced pressure to afford 16.5 g (61%) (E)-3-carboethoxy-4-(2'-bromo-5-isopropylphenyl) -3-butenic acid-tert-butyl ester as a yellow oil. was added dropwise at 0° C. The cooling bath was removed the reaction mixture was stirred overnight at room temperature 20 mL water was added the solvent was removed under reduced pressure The residue was partitioned between water and dichloromethane The organic layers were dried (MgSO4) filtered the solvent was removed under reduced pressure

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a suspension of 1.85 g (77.1 mmol) NaH in 130 mL dry THF, 25.4 g (75.1 mmol) tert-butoxycarbonyl-1-ethoxycarbonylethylidendiethoxy-phosphorane (2) was added dropwise at 0° C., The reaction mixture was stirred for 6 h at 0° C. under Ar. This solution was added under Ar dropwise at 0° C. to 15.5 g (63.5 mmol) 2-bromo-5-isopropoxy-benzaldehyde (1), dissolved in 80 mL dry THF. The cooling bath was removed and the reaction mixture was stirred overnight at room temperature. 20 mL water was added and the solvent was removed under reduced pressure. The residue was partitioned between water and dichloromethane. The organic layers were dried (MgSo4), filtered and the solvent was removed under reduced pressure to afford 16.5 g (61%) (E)-3-carboethoxy-4-(2'-bromo-5-isopropylphenyl)-3-butenic acid-tert-butyl ester as a yellow oil. was added dropwise at 0° C. The cooling bath was removed the reaction mixture was stirred overnight at room temperature 20 mL water was added the solvent was removed under reduced pressure The residue was partitioned between water and dichloromethane The organic layers were dried (MgSo4) filtered the solvent was removed under reduced pressure

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

Procedure: To a suspension of 50.0 g (110 mmol) 3-hydroxybenzaldehyde and 100 g (725 mmol) dry K2CO3 in 100 mL dry DMF, 61.5 g (500 mmol) isopropylbromide was added at room temperature. The reaction mixture was heated for 17 h at 90° C. The solvent was removed under reduced pressure and the residue was partitioned between 2N NaOH and toluene. The collected organic layers were dried (MgSO4), filtered and the solvent removed under pressure. The residue was distilled in vacuo to give 58.8 g (88%) colorless liquid. To a solution of 57.0 g (347 mmol) 3-isopropoxybenzaldehyde in 200 mL dichloromethane 30.5 g (372 mmol) NaOAc was added. After that a solution of 55.5 g (347 mmol) bromine in 50 mL dichloromethane was added dropwise and the reaction mixture was stirred overnight. The reaction mixture was extracted with saturated aqueous Na2SO3 and the combined organic phases were dried (MgSO4), filtered and concentrated under reduced pressure. The residue was distilled in vacuo to give 1 (52.1 g, 62%) as a yellow oil. The reaction mixture was extracted with saturated aqueous Na2SO3 the combined organic phases were dried (MgSO4) filtered concentrated under reduced pressure The residue was distilled in vacuo

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a suspension of 1.85 g (77.1 mmol) NaH in 130 mL dry THF, 25.4 g (75.1 mmol) tert-butoxycarbonyl-1-ethoxycarbonylethylidendiethoxy-phosphorane (2) was added dropwise at 0° C., The reaction mixture was stirred for 6 h at 0° C. under Ar. This solution was added under Ar dropwise at 0° C. to 15.5 g (63.5 mmol) 2-bromo-5-isopropoxy-benzaldehyde (1), dissolved in 80 mL dry THF. The cooling bath was removed and the reaction mixture was stirred overnight at room temperature. 20 mL water was added and the solvent was removed under reduced pressure. The residue was partitioned between water and dichloromethane. The organic layers were dried (MgSO4), filtered and the solvent was removed under reduced pressure to afford 16.5 g (61%) (E)-3-carboethoxy-4-(2'-bromo-5-isopropylphenyl) -3-butenic acid-tert-butyl ester as a yellow oil. was added dropwise at 0° C. The cooling bath was removed the reaction mixture was stirred overnight at room temperature 20 mL water was added the solvent was removed under reduced pressure The residue was partitioned between water and dichloromethane The organic layers were dried (MgSO4) filtered the solvent was removed under reduced pressure