ethyl 2-amino-5,6-difluoro-1,3-dihydroindene-2-carboxylate

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

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

Procedure: To a solution of 2-iodo-3-methyl-benzoic acid (1.50 g, 5.75 mmol), 2-amino-5,6-difluoro-indan-2-carboxylic acid ethyl ester (1.39 g, 5.75 mmol), HATU (2.63 g, 6.90 mmol) in anhydrous DMF (6 mL) is added DIPEA (1.14 mL, 6.90 mmol). The resulting solution is stirred at RT overnight. After the removal of DMF in vacuo, the residue is dissolved in EtOAc (200 mL) and washed with water (1×20 mL) and brine (2×20 mL). The organic layer is dried over anhydrous Na2SO4 and concentrated in vacuo. The residue is purified by flash column chromatography (400 g silica gel, gradient elution: 10%-80% EtOAc in heptane) to give a pure product (156) as white solid (2.32 g, 83%). After the removal of DMF in vacuo the residue is dissolved in EtOAc (200 mL) washed with water (1×20 mL) and brine (2×20 mL) The organic layer is dried over anhydrous Na2SO4 concentrated in vacuo The residue is purified by flash column chromatography (400 g silica gel, gradient elution: 10%-80% EtOAc in heptane)

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

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

Procedure: To a solution of 2-iodo-3-methyl-benzoic acid (1.50 g, 5.75 mmol), 2-amino-5,6-difluoro-indan-2-carboxylic acid ethyl ester (1.39 g, 5.75 mmol), HATU (2.63 g, 6.90 mmol) in anhydrous DMF (6 mL) is added DIPEA (1.14 mL, 6.90 mmol). The resulting solution is stirred at RT overnight. After the removal of DMF in vacuo, the residue is dissolved in EtOAc (200 mL) and washed with water (1×20 mL) and brine (2×20 mL). The organic layer is dried over anhydrous Na2SO4 and concentrated in vacuo. The residue is purified by flash column chromatography (400 g silica gel, gradient elution: 10%-80% EtOAc in heptane) to give a pure product (156) as white solid (2.32 g, 83%). After the removal of DMF in vacuo the residue is dissolved in EtOAc (200 mL) washed with water (1×20 mL) and brine (2×20 mL) The organic layer is dried over anhydrous Na2SO4 concentrated in vacuo The residue is purified by flash column chromatography (400 g silica gel, gradient elution: 10%-80% EtOAc in heptane)