METHYL 2-CHLORO-5-HYDROXYBENZOATE

反応条件: temp:2.51; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Compound (78) (9 g, 48.5 mmol) was subjected to diazotization using NaNO2 (4.5 g 48.5 mmol) in water (50 mL) and H2SO4 (10%, 100 mL). Excess nitrous acid was neutralized with urea. The reaction mixture was poured into a suspension of CuSO4. 5H2O (144 g, 577 mmol) and Cu2O (5.22 g, 41.4 mmol) in water (900 mL) at 0° C. The reaction mixture was stirred for 15 min. at 0-5° C. and was then extracted using diethyl ether (200 mL×3). The organic extract was washed, dried (anhy. Na2SO4), concentrated and purified using a silica gel column and 10% EtOAc in petroleum ether (60-80° C.) as eluant to obtain the title compound(80). at 0° C was then extracted The organic extract was washed dried (anhy Na2SO4), concentrated purified a silica gel column and 10% EtOAc in petroleum ether (60-80° C.) to obtain the title compound(80)

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a suspension of methyl 2-chloro-5-hydroxybenzoate (50 mg) and potassium carbonate (111 mg) in acetone (1 mL) was added 2-iodo-1,1-difluoroethane (35 μL), and the suspension was reacted at 120° C. for 10 minutes in a microwave synthesizer (Biotage, Initiator). After reaction at 130° C. for additional 15 minutes, the reaction mixture was directly purified on silica gel column chromatography to obtain the titled compound (55 mg) as yellow oil. the suspension was reacted at 120° C. for 10 minutes in a microwave synthesizer (Biotage, Initiator) After reaction at 130° C. for additional 15 minutes the reaction mixture was directly purified on silica gel column chromatography

反応条件: temp:2.51; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Compound of example 156 (9 g, 48.5 mmol) was subjected to diazotization using NaNO2 (4.5 g 48.5 mmol) in water (50 mL) and H2SO4 (10%, 100 mL). Excess nitrous acid was neutralized with urea. The reaction mixture was poured into a suspension of CuSO4.5H2O (144 g, 577 mmol) and Cu2O (5.22 g, 41.4 mmol) in water (900 mL) at 0° C. The reaction mixture was stirred for 15 min. at 0-5° C. and was then extracted using diethyl ether (3×200 mL). The organic extract was washed, dried (anhydrous Na2SO4), concentrated and purified using a silica gel column and 10% EtOAc in petroleum ether (60-80° C.) as eluant to obtain the title compound. was then extracted The organic extract was washed dried (anhydrous Na2SO4) concentrated purified a silica gel column and 10% EtOAc in petroleum ether (60-80° C.)

反応条件: temp:2.51; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Compound (78) (9 g, 48.5 mmol) was subjected to diazotization using NaNO2 (4.5 g 48.5 mmol) in water (50 mL) and H2SO4 (10%, 100 mL). Excess nitrous acid was neutralized with urea. The reaction mixture was poured into a suspension of CuSO4. 5H2O (144 g, 577 mmol) and Cu2O (5.22 g, 41.4 mmol) in water (900 mL) at 0° C. The reaction mixture was stirred for 15 min. at 0-5° C. and was then extracted using diethyl ether (200 mL×3). The organic extract was washed, dried (anhy. Na2SO4), concentrated and purified using a silica gel column and 10% EtOAc in petroleum ether (60-80° C.) as eluant to obtain the title compound(80). at 0° C was then extracted The organic extract was washed dried (anhy Na2SO4), concentrated purified a silica gel column and 10% EtOAc in petroleum ether (60-80° C.) to obtain the title compound(80)