5-chloro-3-methyl-2,3-dihydroisoindol-1-one

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

Procedure: Under N2 protection, triethylsilane (23 g, 200 mmol) and trifluoroboron etherate (8.51 g, 60 mmol) were added successively at −15° C. to a mixture of 5-chloro-3-hydroxy-3-methyl-2,3-dihydro-isoindol-1-one and 6-chloro-3-hydroxy-3-methyl-2,3-dihydro-isoindol-1-one (3.95 g, 20 mmol) in dry DCM (100 mL). Afterwards, the reaction mixture was stirred at room temperature for 2 hours and a saturated aqueous solution of NaHCO3 (30 mL) was added. The mixture was then extracted with DCM and the organic layer was washed with brine, dried over anhy. Na2SO4, filtered and concentrated in vacuo to give a crude mixture of products. The two regioisomers were separated by prep-HPLC to give the title compounds, 5-chloro-3-methyl-2,3-dihydro-isoindol-1-one (0.4 g, 11%) and 6-chloro-3-methyl-2,3-dihydro-isoindol-1-one (0.35 g, 9.6%) as white solids. MS: 182.0 (M+H+). The mixture was then extracted with DCM the organic layer was washed with brine dried over anhy Na2SO4, filtered concentrated in vacuo to give a crude mixture of products The two regioisomers were separated by prep-HPLC

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

Procedure: Under N2 protection, triethylsilane (23 g, 200 mmol) and trifluoroboron etherate (8.51 g, 60 mmol) were added successively at −15° C. to a mixture of 5-chloro-3-hydroxy-3-methyl-2,3-dihydro-isoindol-1-one and 6-chloro-3-hydroxy-3-methyl-2,3-dihydro-isoindol-1-one (3.95 g, 20 mmol) in dry DCM (100 mL). Afterwards, the reaction mixture was stirred at room temperature for 2 hours and a saturated aqueous solution of NaHCO3 (30 mL) was added. The mixture was then extracted with DCM and the organic layer was washed with brine, dried over anhy. Na2SO4, filtered and concentrated in vacuo to give a crude mixture of products. The two regioisomers were separated by prep-HPLC to give the title compounds, 5-chloro-3-methyl-2,3-dihydro-isoindol-1-one (0.4 g, 11%) and 6-chloro-3-methyl-2,3-dihydro-isoindol-1-one (0.35 g, 9.6%) as white solids. MS: 182.0 (M+H+). The mixture was then extracted with DCM the organic layer was washed with brine dried over anhy Na2SO4, filtered concentrated in vacuo to give a crude mixture of products The two regioisomers were separated by prep-HPLC

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

Procedure: Under N2 protection, triethylsilane (23 g, 200 mmol) and trifluoroboron etherate (8.51 g, 60 mmol) were added successively at −15° C. to a mixture of 5-chloro-3-hydroxy-3-methyl-2,3-dihydro-isoindol-1-one and 6-chloro-3-hydroxy-3-methyl-2,3-dihydro-isoindol-1-one (3.95 g, 20 mmol) in dry DCM (100 mL). Afterwards, the reaction mixture was stirred at room temperature for 2 hours and a saturated aqueous solution of NaHCO3 (30 mL) was added. The mixture was then extracted with DCM and the organic layer was washed with brine, dried over anhy. Na2SO4, filtered and concentrated in vacuo to give a crude mixture of products. The two regioisomers were separated by prep-HPLC to give the title compounds, 5-chloro-3-methyl-2,3-dihydro-isoindol-1-one (0.4 g, 11%) and 6-chloro-3-methyl-2,3-dihydro-isoindol-1-one (0.35 g, 9.6%) as white solids. MS: 182.0 (M+H+). The mixture was then extracted with DCM the organic layer was washed with brine dried over anhy Na2SO4, filtered concentrated in vacuo to give a crude mixture of products The two regioisomers were separated by prep-HPLC