5-fluoro-2-phenylmethoxybenzaldehyde

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

Conditions: temp:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To the Grignard Solution A cooled to −78° C., a solution of 2-benzyloxy-5-fluoro-benzaldehyde (879 mg, 3.82 mmol, 1.0 eq.) in THF (10 mL) was added dropwise. The mixture was stirred at −78° C. for 1 hour and further at r.t. for 18 hours. The reaction was carefully quenched with 1M aq. NH4Cl soln. (50 mL) and AcOEt (100 mL) was added. The resulting suspension was filtered through celite and the filter cake was rinsed with water and AcOEt. The layers were separated and the aq. phase was extracted with AcOEt (2×150 mL). The comb. org. phases were washed with sat. aq. NaCl soln. (1×100 mL), dried over MgSO4, and concentrated in vacuo. The residue was purified by flash master (column: 100 g, flow: 45 mL/min, Heptane to Heptane+45% AcOEt) to yield (±)-3-(2-benzyloxy-5-fluoro-phenyl)-3H-isobenzofuran-1-one as a white solid. The reaction was carefully quenched with 1M aq. NH4Cl soln (50 mL) and AcOEt (100 mL) was added The resulting suspension was filtered through celite the filter cake was rinsed with water and AcOEt The layers were separated the aq. phase was extracted with AcOEt (2×150 mL) phases were washed with sat. aq. NaCl soln (1×100 mL), dried over MgSO4 concentrated in vacuo The residue was purified by flash master (column: 100 g, flow: 45 mL/min, Heptane to Heptane+45% AcOEt)

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

Procedure: To a mixture of 5-fluoro-2-hydroxybenzaldehyde (5.0 g, 35.69 mmol, 1.00 eq.) and potassium carbonate (7.97 g, 57.10 mmol, 1.60 eq.) in DMF (60 mL), benzyl bromide (4.54 mL, 37.47 mmol, 1.05 eq.) was added dropwise. The reaction mixture was refluxed for 2 hours, then allowed to cool to r.t. and poured into 100 mL of cold water and extracted with AcOEt. The organic extract was washed with 10% aq. NaOH soln. and sat. aq. NaCl soln., dried over MgSO4 and concentrated in vacuo. The residue was purified by flash master (column: 100 g, flow: 45 mL/min, Heptane to Heptane+30% AcOEt) to yield 2-benzyloxy-5-fluoro-benzaldehyde as an yellow oil. was added dropwise The reaction mixture was refluxed for 2 hours extracted with AcOEt The organic extract was washed with 10% aq. NaOH soln , dried over MgSO4 concentrated in vacuo The residue was purified by flash master (column: 100 g, flow: 45 mL/min, Heptane to Heptane+30% AcOEt)