2,2-dimethyl-3H-1-benzofuran-7-carbonyl chloride

反応条件: temp:0.00; pressure:0.00; stir:

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

実験手順: A test tube (25×150 mm) containing a stirring bar and 2-amino-indane-2-carboxylic acid ethyl ester (0.5 g, 2.436 mmol) is charged with dry DCM (3 mL). Stirring is initiated. After dissolution, the DIPEA (1.50 mL, 8.6 mmol) and 4-dimethylaminopyridine (2 mg, 17 μmol) are added. A solution of 2,2-dimethyl-2,3-dihydro-1-benzofuran-7-carbonyl chloride (0.73 g, 3.47 mmol) in dry DCM (4 mL) is added to the reaction tube. After stirring for 18 h, tlc analysis (silica, 10% CH3OH in DCM) indicates complete consumption of the starting amine. The reaction mixture is diluted with DCM (10 mL) and washed with 5% aqueous HCl (2×5 mL) and brine (5 mL), dried over MgSO4 filtered and evaporated by pumping to constant weight gives 0.72 g of a light brown gum. This material is purified by chromatography (silica, 0% to 20% EtOAc in DCM) on the ISCO Companion using a 40 g cartridge (silica). Fractions 17-22 are combined, evaporated and pumped to a constant weight to provide 0.62 g (67%) of a glassy solid. A test tube (25×150 mm) containing a stirring bar After dissolution After stirring for 18 h consumption of the starting amine The reaction mixture is diluted with DCM (10 mL) washed with 5% aqueous HCl (2×5 mL) and brine (5 mL) dried over MgSO4 filtered evaporated

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

実験手順: To a solution of the product of Example 126A (0.20 g, 1.1 mmol) and Et3N (0.45 mL, 3.2 mmol) in 30 mL THF was added 2,2-dimethyl-2,3-dihydro-1-benzofuran-7-carbonyl chloride (Acros, 0.34 g, 1.6 mmol). This mixture was warmed to reflux and allowed to stir for 2 hours. The mixture was then cooled to ambient temperature and concentrated under reduced pressure. The residue was diluted with 10 mL EtOAc and washed with 5 mL saturated, aqueous NH4Cl. The layers were separated and the aqueous layer was extracted 2×5 mL EtOAc. The combined organics were dried over anhydrous Na2SO4, filtered, concentrated under reduced pressure and purified via flash column chromatography (SiO2, 4:1 hexanes:EtOAc) to provide the title compound (0.21 mmol, 0.57 mmol, 53% yield). 1H NMR (300 MHz, CDCl3) δ ppm 1.55 (s, 6H), 2.22 (s, 3H), 2.27 (s, 3H), 3.02 (s, 2H), 3.31 (s, 3H), 3.77-3.89 (m, 2H), 4.33-4.50 (m, 2H), 6.85 (t, J=7.5 Hz, 1H), 7.22 (d, J=7.5 Hz, 1H), 8.00 (d, J=8.1 Hz, 1H); MS (DCI/NH3) m/z 361 (M+H)+; Anal. calculated for C19H24N2O3S: C, 63.31; H, 6.71; N, 7.77. Found: C, 63.19; H, 6.50; N, 7.66. This mixture was warmed to reflux concentrated under reduced pressure The residue was diluted with 10 mL EtOAc washed with 5 mL saturated The layers were separated the aqueous layer was extracted 2×5 mL EtOAc The combined organics were dried over anhydrous Na2SO4 filtered concentrated under reduced pressure purified via flash column chromatography (SiO2, 4:1 hexanes:EtOAc)

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

実験手順: To a solution of the product of Example 126A (0.20 g, 1.1 mmol) and Et3N (0.45 mL, 3.2 mmol) in 30 mL THF was added 2,2-dimethyl-2,3-dihydro-1-benzofuran-7-carbonyl chloride (Acros, 0.34 g, 1.6 mmol). This mixture was warmed to reflux and allowed to stir for 2 hours. The mixture was then cooled to ambient temperature and concentrated under reduced pressure. The residue was diluted with 10 mL EtOAc and washed with 5 mL saturated, aqueous NH4Cl. The layers were separated and the aqueous layer was extracted 2×5 mL EtOAc. The combined organics were dried over anhydrous Na2SO4, filtered, concentrated under reduced pressure and purified via flash column chromatography (SiO2, 4:1 hexanes:EtOAc) to provide the title compound (0.21 mmol, 0.57 mmol, 53% yield). 1H NMR (300 MHz, CDCl3) δ ppm 1.55 (s, 6H), 2.22 (s, 3H), 2.27 (s, 3H), 3.02 (s, 2H), 3.31 (s, 3H), 3.77-3.89 (m, 2H), 4.33-4.50 (m, 2H), 6.85 (t, J=7.5 Hz, 1H), 7.22 (d, J=7.5 Hz, 1H), 8.00 (d, J=8.1 Hz, 1H); MS (DCI/NH3) m/z 361 (M+H)+; Anal. calculated for C19H24N2O3S: C, 63.31; H, 6.71; N, 7.77. Found: C, 63.19; H, 6.50; N, 7.66. This mixture was warmed to reflux concentrated under reduced pressure The residue was diluted with 10 mL EtOAc washed with 5 mL saturated The layers were separated the aqueous layer was extracted 2×5 mL EtOAc The combined organics were dried over anhydrous Na2SO4 filtered concentrated under reduced pressure purified via flash column chromatography (SiO2, 4:1 hexanes:EtOAc)

反応条件: temp:0.00; pressure:0.00; stir:

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

実験手順: To a solution of the product of Example 126A (0.20 g, 1.1 mmol) and Et3N (0.45 mL, 3.2 mmol) in 30 mL THF was added 2,2-dimethyl-2,3-dihydro-1-benzofuran-7-carbonyl chloride (Acros, 0.34 g, 1.6 mmol). This mixture was warmed to reflux and allowed to stir for 2 hours. The mixture was then cooled to ambient temperature and concentrated under reduced pressure. The residue was diluted with 10 mL EtOAc and washed with 5 mL saturated, aqueous NH4Cl. The layers were separated and the aqueous layer was extracted 2×5 mL EtOAc. The combined organics were dried over anhydrous Na2SO4, filtered, concentrated under reduced pressure and purified via flash column chromatography (SiO2, 4:1 hexanes:EtOAc) to provide the title compound (0.21 mmol, 0.57 mmol, 53% yield). 1H NMR (300 MHz, CDCl3) δ ppm 1.55 (s, 6H), 2.22 (s, 3H), 2.27 (s, 3H), 3.02 (s, 2H), 3.31 (s, 3H), 3.77-3.89 (m, 2H), 4.33-4.50 (m, 2H), 6.85 (t, J=7.5 Hz, 1H), 7.22 (d, J=7.5 Hz, 1H), 8.00 (d, J=8.1 Hz, 1H); MS (DCI/NH3) m/z 361 (M+H); Anal. calculated for C19H24N2O3S: C, 63.31; H, 6.71; N, 7.77. Found: C, 63.19; H, 6.50; N, 7.66. This mixture was warmed to reflux concentrated under reduced pressure The residue was diluted with 10 mL EtOAc washed with 5 mL saturated The layers were separated the aqueous layer was extracted 2×5 mL EtOAc The combined organics were dried over anhydrous Na2SO4 filtered concentrated under reduced pressure purified via flash column chromatography (SiO2, 4:1 hexanes:EtOAc)

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

実験手順: A test tube (25×150 mm) containing a stirring bar and 2-amino-indane-2-carboxylic acid ethyl ester (0.5 g, 2.436 mmol) is charged with dry DCM (3 mL). Stirring is initiated. After dissolution, the DIPEA (1.50 mL, 8.6 mmol) and 4-dimethylaminopyridine (2 mg, 17 μmol) are added. A solution of 2,2-dimethyl-2,3-dihydro-1-benzofuran-7-carbonyl chloride (0.73 g, 3.47 mmol) in dry DCM (4 mL) is added to the reaction tube. After stirring for 18 h, tlc analysis (silica, 10% CH3OH in DCM) indicates complete consumption of the starting amine. The reaction mixture is diluted with DCM (10 mL) and washed with 5% aqueous HCl (2×5 mL) and brine (5 mL), dried over MgSO4 filtered and evaporated by pumping to constant weight gives 0.72 g of a light brown gum. This material is purified by chromatography (silica, 0% to 20% EtOAc in DCM) on the ISCO Companion using a 40 g cartridge (silica). Fractions 17-22 are combined, evaporated and pumped to a constant weight to provide 0.62 g (67%) of a glassy solid. A test tube (25×150 mm) containing a stirring bar After dissolution After stirring for 18 h consumption of the starting amine The reaction mixture is diluted with DCM (10 mL) washed with 5% aqueous HCl (2×5 mL) and brine (5 mL) dried over MgSO4 filtered evaporated

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

実験手順: To a solution of the product of Example 126A (0.20 g, 1.1 mmol) and Et3N (0.45 mL, 3.2 mmol) in 30 mL THF was added 2,2-dimethyl-2,3-dihydro-1-benzofuran-7-carbonyl chloride (Acros, 0.34 g, 1.6 mmol). This mixture was warmed to reflux and allowed to stir for 2 hours. The mixture was then cooled to ambient temperature and concentrated under reduced pressure. The residue was diluted with 10 mL EtOAc and washed with 5 mL saturated, aqueous NH4Cl. The layers were separated and the aqueous layer was extracted 2×5 mL EtOAc. The combined organics were dried over anhydrous Na2SO4, filtered, concentrated under reduced pressure and purified via flash column chromatography (SiO2, 4:1 hexanes:EtOAc) to provide the title compound (0.21 mmol, 0.57 mmol, 53% yield). 1H NMR (300 MHz, CDCl3) δ ppm 1.55 (s, 6H), 2.22 (s, 3H), 2.27 (s, 3H), 3.02 (s, 2H), 3.31 (s, 3H), 3.77-3.89 (m, 2H), 4.33-4.50 (m, 2H), 6.85 (t, J=7.5 Hz, 1H), 7.22 (d, J=7.5 Hz, 1H), 8.00 (d, J=8.1 Hz, 1H); MS (DCI/NH3) m/z 361 (M+H)+; Anal. calculated for C19H24N2O3S: C, 63.31; H, 6.71; N, 7.77. Found: C, 63.19; H, 6.50; N, 7.66. This mixture was warmed to reflux concentrated under reduced pressure The residue was diluted with 10 mL EtOAc washed with 5 mL saturated The layers were separated the aqueous layer was extracted 2×5 mL EtOAc The combined organics were dried over anhydrous Na2SO4 filtered concentrated under reduced pressure purified via flash column chromatography (SiO2, 4:1 hexanes:EtOAc)