5-fluoro-3,4-dihydro-2H-chromen-4-ol

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

Procedure: To a stirred mixture of 1,1-dimethylethl 6-[(dimethylamino)carbonyl]-4-hydroxy-2-methyl-1H-benzimidazole-1-carboxylate (1.00 g, 3.13 mmol, STEP 2), 5-fluoro-3,4-dihydro-2H-chromen-4-ol (948 mg, 5.64 mmol, STEP 3-1) and triphenylphosphine (2.57 g, 9.79 mmol) in toluene (50 mL) was added diisopropyl azodicarboxylate (DIAD) (1.98 g, 4.90 mmol) at room temperature. The reaction mixture was stirred at room temperature for 2 hours and concentrated in vacuum. The residue was dissolved in tetrahydrofuran (30 mL) and methanol (15 mL), and sodium hydroxide (750 mg, 18.8 mmol) was added to the mixture at room temperature. After stirring at room temperature for 1 hour, the mixture was quenched with saturated sodium dihydrogenphosphate aqueous solution, and extracted with ethyl acetate. The organic layers were combined, dried over magnesium sulfate and concentrated in vacuum. The residue was purified by column chromatography on silica gel (dichloromethane only then ethyl acetate methanol 10:1 as an eluent) to afford the title compound as a white solid (510 mg, 50%). concentrated in vacuum The residue was dissolved in tetrahydrofuran (30 mL) After stirring at room temperature for 1 hour the mixture was quenched with saturated sodium dihydrogenphosphate aqueous solution extracted with ethyl acetate dried over magnesium sulfate concentrated in vacuum The residue was purified by column chromatography on silica gel (dichloromethane only

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

Procedure: To a stirred mixture of 1,1-dimethylethl 6-[(dimethylamino)carbonyl]-4-hydroxy-2-methyl-1H-benzimidazole-1-carboxylate (1.00 g, 3.13 mmol, STEP 2), 5-fluoro-3,4-dihydro-2H-chromen-4-ol (948 mg, 5.64 mmol, STEP 3-1) and triphenylphosphine (2.57 g, 9.79 mmol) in toluene (50 mL) was added diisopropyl azodicarboxylate (DIAD) (1.98 g, 4.90 mmol) at room temperature. The reaction mixture was stirred at room temperature for 2 hours and concentrated in vacuum. The residue was dissolved in tetrahydrofuran (30 mL) and methanol (15 mL), and sodium hydroxide (750 mg, 18.8 mmol) was added to the mixture at room temperature. After stirring at room temperature for 1 hour, the mixture was quenched with saturated sodium dihydrogenphosphate aqueous solution, and extracted with ethyl acetate. The organic layers were combined, dried over magnesium sulfate and concentrated in vacuum. The residue was purified by column chromatography on silica gel (dichloromethane only then ethyl acetate methanol 10:1 as an eluent) to afford the title compound as a white solid (510 mg, 50%). concentrated in vacuum The residue was dissolved in tetrahydrofuran (30 mL) After stirring at room temperature for 1 hour the mixture was quenched with saturated sodium dihydrogenphosphate aqueous solution extracted with ethyl acetate dried over magnesium sulfate concentrated in vacuum The residue was purified by column chromatography on silica gel (dichloromethane only

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

Procedure: To a stirred mixture of 1,1-dimethylethl 6-[(dimethylamino)carbonyl]-4-hydroxy-2-methyl-1H-benzimidazole-1-carboxylate (1.00 g, 3.13 mmol, STEP 2), 5-fluoro-3,4-dihydro-2H-chromen-4-ol (948 mg, 5.64 mmol, STEP 3-1) and triphenylphosphine (2.57 g, 9.79 mmol) in toluene (50 mL) was added diisopropyl azodicarboxylate (DIAD) (1.98 g, 4.90 mmol) at room temperature. The reaction mixture was stirred at room temperature for 2 hours and concentrated in vacuum. The residue was dissolved in tetrahydrofuran (30 mL) and methanol (15 mL), and sodium hydroxide (750 mg, 18.8 mmol) was added to the mixture at room temperature. After stirring at room temperature for 1 hour, the mixture was quenched with saturated sodium dihydrogenphosphate aqueous solution, and extracted with ethyl acetate. The organic layers were combined, dried over magnesium sulfate and concentrated in vacuum. The residue was purified by column chromatography on silica gel (dichloromethane only then ethyl acetate methanol 10:1 as an eluent) to afford the title compound as a white solid (510 mg, 50%). concentrated in vacuum The residue was dissolved in tetrahydrofuran (30 mL) After stirring at room temperature for 1 hour the mixture was quenched with saturated sodium dihydrogenphosphate aqueous solution extracted with ethyl acetate dried over magnesium sulfate concentrated in vacuum The residue was purified by column chromatography on silica gel (dichloromethane only