methyl 2-methyl-3-oxo-1H-indene-2-carboxylate

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

Procedure: A solution of the methyl 2-methyl-1-oxo-2,3-dihydro-1H-indene-2-carboxylate (2.04 g, 9.99 mmol) in glacial acetic acid (22 mL) and concentrated H2SO4 (2 mL) was hydrogenated on a Parr apparatus under 50 psi of hydrogen using 10% palladium on carbon (50% H2O, 0.200 g) as the catalyst. After 4 hours the reaction was filtered to remove the catalyst and washed 2× methanol, then concentrated to remove most of the acetic acid. The residue was neutralized using saturated Na2CO3 and the organics extracted twice with 25 mL ethyl acetate, then the combined organics washed with brine, dried (Na2SO4), filtered and concentrated to 2.0 g of methyl 2-methyl-2,3-dihydro-1H-indene-2-carboxylate. After 4 hours the reaction was filtered to remove the catalyst washed 2× methanol concentrated to remove most of the acetic acid the organics extracted twice with 25 mL ethyl acetate the combined organics washed with brine dried (Na2SO4) filtered concentrated to 2.0 g of methyl 2-methyl-2,3-dihydro-1H-indene-2-carboxylate

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

Procedure: To a flask cooled at 0 degrees Centigrade containing diisopropylamine (2.06 mL, 14.58 mmol) in tetrahydrofuran (14 mL) was added dropwise over 15 minutes a solution of n-butyl lithium (5.55 mL of 2.5 M in hexanes, 14.58 mmol). This mixture was stirred for 30 min. A second flask containing the 2-methyl-1-indanone (2.03 g, 13.89 mmol) in tetrahydrofuran (10 mL) was cooled to −78 degrees Centigrade under N2. The freshly prepared lithium diisopropylethylamide was cooled to −78 degrees centigrade and added drop wise via cannula. The orangish mixture became somewhat heterogeneous over 30 minutes and then neat methyl cyanoformate (1.32 mL, 16.66 mmol) was added and the reaction mixture stirred an additional 40 minutes while allowing the reaction to warm to −20 degrees centigrade. The reaction was quenched with saturated aqueous NH4Cl solution and the organics extracted 2×25 mL diethyl ether, washed one time in brine, then dried (Na2SO4), filtered and concentrated to give methyl 2-methyl-1-oxo-2,3-dihydro-1H-indene-2-carboxylate. No further purification was necessary. To a flask cooled at 0 degrees Centigrade was cooled to −78 degrees Centigrade under N2 added drop wise via cannula The orangish mixture became somewhat heterogeneous over 30 minutes the reaction mixture stirred an additional 40 minutes the reaction to warm to −20 degrees centigrade The reaction was quenched with saturated aqueous NH4Cl solution the organics extracted 2×25 mL diethyl ether washed one time in brine dried (Na2SO4) filtered concentrated

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

Procedure: To a flask cooled at 0 degrees Centigrade containing diisopropylamine (2.06 mL, 14.58 mmol) in tetrahydrofuran (14 mL) was added dropwise over 15 minutes a solution of n-butyl lithium (5.55 mL of 2.5 M in hexanes, 14.58 mmol). This mixture was stirred for 30 min. A second flask containing the 2-methyl-1-indanone (2.03 g, 13.89 mmol) in tetrahydrofuran (10 mL) was cooled to −78 degrees Centigrade under N2. The freshly prepared lithium diisopropylethylamide was cooled to −78 degrees centigrade and added drop wise via cannula. The orangish mixture became somewhat heterogeneous over 30 minutes and then neat methyl cyanoformate (1.32 mL, 16.66 mmol) was added and the reaction mixture stirred an additional 40 minutes while allowing the reaction to warm to −20 degrees centigrade. The reaction was quenched with saturated aqueous NH4Cl solution and the organics extracted 2×25 mL diethyl ether, washed one time in brine, then dried (Na2SO4), filtered and concentrated to give methyl 2-methyl-1-oxo-2,3-dihydro-1H-indene-2-carboxylate. No further purification was necessary. To a flask cooled at 0 degrees Centigrade was cooled to −78 degrees Centigrade under N2 added drop wise via cannula The orangish mixture became somewhat heterogeneous over 30 minutes the reaction mixture stirred an additional 40 minutes the reaction to warm to −20 degrees centigrade The reaction was quenched with saturated aqueous NH4Cl solution the organics extracted 2×25 mL diethyl ether washed one time in brine dried (Na2SO4) filtered concentrated

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

Procedure: A mixture of the methyl 2-methyl-1-oxo-2,3-dihydro-1H-indene-2-carboxylate (2.04 g, 9.99 mmol) and 10% Pd/C (0.200 g; wet) in HOAc/conc H2SO4 (22/2 mL respectively) was hydrogenated under 50 psi H2 for 4 h using a Parr hydrogenation apparatus. The mixture was filtered through Celite (2×MeOH wash) and the filtrate was partially concentrated in vacuo. The residue was neutralized with satd Na2CO3 and the whole was extracted with EtOAc (2×25 mL). Combined organics were washed with brine, dried over Na2SO4 and concentrated in vacuo affording the title compound. 1H NMR (400 MHz, CDCl3) δ ppm 1.35 (s, 3H), 2.81 (d, J=15.6 Hz, 2H), 3.47 (d, J=15.6 Hz, 2H), 3.71 (s, 3H), 7.12-7.23 (m, 4H). The mixture was filtered through Celite (2×MeOH wash) the filtrate was partially concentrated in vacuo the whole was extracted with EtOAc (2×25 mL) Combined organics were washed with brine dried over Na2SO4 concentrated in vacuo

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

Procedure: A mixture of the methyl 2-methyl-1-oxo-2,3-dihydro-1H-indene-2-carboxylate (2.04 g, 9.99 mmol) and 10% Pd/C (0.200 g; wet) in HOAc/conc H2SO4 (22/2 mL respectively) was hydrogenated under 50 psi H2 for 4 h using a Parr hydrogenation apparatus. The mixture was filtered through Celite (2×MeOH wash) and the filtrate was partially concentrated in vacuo. The residue was neutralized with satd Na2CO3 and the whole was extracted with EtOAc (2×25 mL). Combined organics were washed with brine, dried over Na2SO4 and concentrated in vacuo affording the title compound. 1H NMR (400 MHz, CDCl3) δ ppm 1.35 (s, 3H), 2.81 (d, J=15.6 Hz, 2H), 3.47 (d, J=15.6 Hz, 2H), 3.71 (s, 3H), 7.12-7.23 (m, 4H). The mixture was filtered through Celite (2×MeOH wash) the filtrate was partially concentrated in vacuo the whole was extracted with EtOAc (2×25 mL) Combined organics were washed with brine dried over Na2SO4 concentrated in vacuo

Conditions: temp:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of diisopropylamine (2.06 mL, 14.6 mmol) in THF (14 mL) at 0° C. was a solution of n-butyl lithium (5.55 mL of a 2.5 M in solution in hexanes; 14.6 mmol), dropwise over 15 min. Meanwhile, a solution of 2-methyl-1-indanone (2.03 g, 13.9 mmol) in THF (10 mL) was prepared and cooled to −78° C. under N2. After 30 minutes the above solution of LDA was cooled to −78° C. and added to the above solution of indanone, dropwise over 15 min via double-ended needle. The mixture was stirred 30 min and methyl cyanoformate (1.32 mL, 16.7 mmol) was added. The mixture was stirred 40 minutes, gradually warming ca. to −20° C., quenched with satd NH4Cl and extracted with Et2O (2×25 mL). Combined organics were washed (brine), dried over Na2SO4 and concentrated in vacuo, affording the title compound which was used without further purification. 1H NMR (400 MHz, CDCl3) δ ppm 1.52 (s, 3H), 3.00 (d, J=17.3 Hz, 1H), 3.67-3.73 (m, 4H), 7.41 (t, J=7.57 Hz, 1H), 7.47 (m, 1H), 7.63 (m, 1H), 7.79 (d, J=7.57 Hz, 1H). at 0° C. The mixture was stirred 40 minutes gradually warming ca. to −20° C. quenched with satd NH4Cl extracted with Et2O (2×25 mL) Combined organics were washed (brine) dried over Na2SO4 concentrated in vacuo

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

Procedure: A mixture of the methyl 2-methyl-1-oxo-2,3-dihydro-1H-indene-2-carboxylate (2.04 g, 9.99 mmol) and 10% Pd/C (0.200 g; wet) in HOAc/conc H2SO4 (22/2 mL respectively) was hydrogenated under 50 psi H2 for 4 h using a Parr hydrogenation apparatus. The mixture was filtered through Celite (2×MeOH wash) and the filtrate was partially concentrated in vacuo. The residue was neutralized with satd Na2CO3 and the whole was extracted with EtOAc (2×25 mL). Combined organics were washed with brine, dried over Na2SO4 and concentrated in vacuo affording the title compound. 1H NMR (400 MHz, CDCl3) δ ppm 1.35 (s, 3H), 2.81 (d, J=15.6 Hz, 2 H), 3.47 (d, J=15.6 Hz, 2 H), 3.71 (s, 3H), 7.12-7.23 (m, 4H). The mixture was filtered through Celite (2×MeOH wash) the filtrate was partially concentrated in vacuo the whole was extracted with EtOAc (2×25 mL) Combined organics were washed with brine dried over Na2SO4 concentrated in vacuo

Conditions: temp:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of diisopropylamine (2.06 mL, 14.6 mmol) in THF (14 mL) at 0° C. was a solution of n-butyl lithium (5.55 mL of a 2.5 M in solution in hexanes; 14.6 mmol), dropwise over 15 min. Meanwhile, a solution of 2-methyl-1-indanone (2.03 g, 13.9 mmol) in THF (10 mL) was prepared and cooled to −78° C. under N2. After 30 minutes the above solution of LDA was cooled to −78° C. and added to the above solution of indanone, dropwise over 15 min via double-ended needle. The mixture was stirred 30 min and methyl cyanoformate (1.32 mL, 16.7 mmol) was added. The mixture was stirred 40 minutes, gradually warming ca. to −20° C., quenched with satd NH4Cl and extracted with Et2O (2×25 mL). Combined organics were washed (brine), dried over Na2SO4 and concentrated in vacuo, affording the title compound which was used without further purification. 1H NMR (400 MHz, CDCl3) δ ppm 1.52 (s, 3H), 3.00 (d, J=17.3 Hz, 1 H), 3.67-3.73 (m, 4H), 7.41 (t, J=7.57 Hz, 1H), 7.47 (m, 1H), 7.63 (m, 1 H), 7.79 (d, J=7.57 Hz, 1 H). at 0° C. The mixture was stirred 40 minutes gradually warming ca. to −20° C. quenched with satd NH4Cl extracted with Et2O (2×25 mL) Combined organics were washed (brine) dried over Na2SO4 concentrated in vacuo

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

Procedure: A solution of the methyl 2-methyl-1-oxo-2,3-dihydro-1H-indene-2-carboxylate (2.04 g, 9.99 mmol) in glacial acetic acid (22 mL) and concentrated H2SO4 (2 mL) was hydrogenated on a Parr apparatus under 50 psi of hydrogen using 10% palladium on carbon (50% H2O, 0.200 g) as the catalyst. After 4 hours the reaction was filtered to remove the catalyst and washed 2× methanol, then concentrated to remove most of the acetic acid. The residue was neutralized using saturated Na2CO3 and the organics extracted twice with 25 mL ethyl acetate, then the combined organics washed with brine, dried (Na2SO4), filtered and concentrated to 2.0 g of methyl 2-methyl-2,3-dihydro-1H-indene-2-carboxylate. After 4 hours the reaction was filtered to remove the catalyst washed 2× methanol concentrated to remove most of the acetic acid the organics extracted twice with 25 mL ethyl acetate the combined organics washed with brine dried (Na2SO4) filtered concentrated to 2.0 g of methyl 2-methyl-2,3-dihydro-1H-indene-2-carboxylate

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

Procedure: To a flask cooled at 0 degrees Centigrade containing diisopropylamine (2.06 mL, 14.58 mmol) in tetrahydrofuran (14 mL) was added dropwise over 15 minutes a solution of n-butyl lithium (5.55 mL of 2.5 M in hexanes, 14.58 mmol). This mixture was stirred for 30 min. A second flask containing the 2-methyl-1-indanone (2.03 g, 13.89 mmol) in tetrahydrofuran (10 mL) was cooled to −78 degrees Centigrade under N2. The freshly prepared lithium diisopropylethylamide was cooled to −78 degrees centigrade and added drop wise via cannula. The orangish mixture became somewhat heterogeneous over 30 minutes and then neat methyl cyanoformate (1.32 mL, 16.66 mmol) was added and the reaction mixture stirred an additional 40 minutes while allowing the reaction to warm to −20 degrees centigrade. The reaction was quenched with saturated aqueous NH4Cl solution and the organics extracted 2×25 mL diethyl ether, washed one time in brine, then dried (Na2SO4), filtered and concentrated to give methyl 2-methyl-1-oxo-2,3-dihydro-1H-indene-2-carboxylate. No further purification was necessary. To a flask cooled at 0 degrees Centigrade was cooled to −78 degrees Centigrade under N2 added drop wise via cannula The orangish mixture became somewhat heterogeneous over 30 minutes the reaction mixture stirred an additional 40 minutes the reaction to warm to −20 degrees centigrade The reaction was quenched with saturated aqueous NH4Cl solution the organics extracted 2×25 mL diethyl ether washed one time in brine dried (Na2SO4) filtered concentrated

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

Procedure: A mixture of the methyl 2-methyl-1-oxo-2,3-dihydro-1H-indene-2-carboxylate (2.04 g, 9.99 mmol) and 10% Pd/C (0.200 g; wet) in HOAc/conc H2SO4 (22/2 mL respectively) was hydrogenated under 50 psi H2 for 4 h using a Parr hydrogenation apparatus. The mixture was filtered through Celite (2×MeOH wash) and the filtrate was partially concentrated in vacuo. The residue was neutralized with satd Na2CO3 and the whole was extracted with EtOAc (2×25 mL). Combined organics were washed with brine, dried over Na2SO4 and concentrated in vacuo affording the title compound. 1H NMR (400 MHz, CDCl3) δ ppm 1.35 (s, 3H), 2.81 (d, J=15.6 Hz, 2H), 3.47 (d, J=15.6 Hz, 2H), 3.71 (s, 3H), 7.12-7.23 (m, 4H). The mixture was filtered through Celite (2×MeOH wash) the filtrate was partially concentrated in vacuo the whole was extracted with EtOAc (2×25 mL) Combined organics were washed with brine dried over Na2SO4 concentrated in vacuo

Conditions: temp:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of diisopropylamine (2.06 mL, 14.6 mmol) in THF (14 mL) at 0° C. was a solution of n-butyl lithium (5.55 mL of a 2.5 M in solution in hexanes; 14.6 mmol), dropwise over 15 min. Meanwhile, a solution of 2-methyl-1-indanone (2.03 g, 13.9 mmol) in THF (10 mL) was prepared and cooled to −78° C. under N2. After 30 minutes the above solution of LDA was cooled to −78° C. and added to the above solution of indanone, dropwise over 15 min via double-ended needle. The mixture was stirred 30 min and methyl cyanoformate (1.32 mL, 16.7 mmol) was added. The mixture was stirred 40 minutes, gradually warming ca. to −20° C., quenched with satd NH4Cl and extracted with Et2O (2×25 mL). Combined organics were washed (brine), dried over Na2SO4 and concentrated in vacuo, affording the title compound which was used without further purification. 1H NMR (400 MHz, CDCl3) δ ppm 1.52 (s, 3H), 3.00 (d, J=17.3 Hz, 1H), 3.67-3.73 (m, 4H), 7.41 (t, J=7.57 Hz, 1H), 7.47 (m, 1H), 7.63 (m, 1H), 7.79 (d, J=7.57 Hz, 1H). at 0° C. The mixture was stirred 40 minutes gradually warming ca. to −20° C. quenched with satd NH4Cl extracted with Et2O (2×25 mL) Combined organics were washed (brine) dried over Na2SO4 concentrated in vacuo