methyl 2-methyl-1,3-dihydroindene-2-carboxylate

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

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

Procedure: Indane-2-carboxylic acid methyl ester (550 mg, 3.125 mmol) was dissolved in THF (20 mL). At −78° C. LiHMDS (1M solution in THF, 3.75 mL) was added into the reaction mixture. The solution was stirred for 15 min at −78° C., warmed to 0° C. for 15 min and then −78° C. for an additional 15 min. Methyl iodide (250 μL, 4.01 mmol) was then added into the reaction mixture followed by stirring at −78° C. for 15 min, room temperature for 30 min and then quenched with saturated ammonium chloride. The solution was then diluted with diethyl ether and washed with saturated sodium bicarbonate, brine, dried (MgSO4), filtered and concentrated. The crude mixture was then purified by silica gel flash column chromatography to afford 2-methyl-indan-2-carboxylic acid methyl ester (52 mg, 9%) as a white solid. 1H NMR (400 MHz, CDCl3) 7.16 (m, 4H), 3.72 (t, 3H), 3.48 (d, 2H), 2.81 (d, 2H), 1.36 (s, 3H). At −78° C warmed to 0° C. for 15 min −78° C. for an additional 15 min by stirring at −78° C. for 15 min, room temperature for 30 min quenched with saturated ammonium chloride The solution was then diluted with diethyl ether washed with saturated sodium bicarbonate, brine dried (MgSO4) filtered concentrated The crude mixture was then purified by silica gel flash column chromatography

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

Procedure: To a tetrahydrofuran/H2O/methanol (4 mL/1 mL/1 mL) solution of the methyl 2-methyl-2,3-dihydro-1H-indene-2-carboxylate (1.80 g, 9.46 mmol) was added lithium hydroxide monohydrate (1.19 g, 28.39 mmol). The reaction mixture stirred at ambient temperature for 4 hours and then the mixture was acidified to pH 3 using 1N HCl. The organics were extracted twice with 25 mL diethyl ether, the combined organics were washed with brine and then dried (Na2SO4), filtered and concentrated to as 2-Methyl-2,3-dihydro-1H-indene-2-carboxylic acid a white solid. The organics were extracted twice with 25 mL diethyl ether the combined organics were washed with brine dried (Na2SO4) filtered concentrated to as 2-Methyl-2,3-dihydro-1H-indene-2-carboxylic acid a white solid

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 solution of methyl 2-methyl-2,3-dihydro-1H-indene-2-carboxylate (1.80 g, 9.46 mmol) in THF/water/MeOH (4/1/1 mL respectively) was added lithium hydroxide monohydrate (1.19 g, 28.4 mmol). The reaction mixture stirred at ambient temperature 4 h, acidified to pH 3 with 1 N HCl and extracted with Et2O (2×25 mL). Combined organics were washed (water, brine), dried over Na2SO4 and concentrated in vacuo affording the title compound as a white solid. 1H NMR (400 MHz, CDCl3) δ ppm 1.39 (s, 3H), 2.83 (d, J=15.9 Hz, 2H), 3.50 (d, J=15.9 Hz, 2H), 7.12-7.23 (m, 4H). extracted with Et2O (2×25 mL) Combined organics were washed (water, 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: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:

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

Procedure: Indane-2-carboxylic acid methyl ester (550 mg, 3.125 mmol) was dissolved in THF (20 mL). At −78° C. LiHMDS (1M solution in THF, 3.75 mL) was added into the reaction mixture. The solution was stirred for 15 min at −78° C., warmed to 0° C. for 15 min and then −78° C. for an additional 15 min. Methyl iodide (250 μL, 4.01 mmol) was then added into the reaction mixture followed by stirring at −78° C. for 15 min, room temperature for 30 min and then quenched with saturated ammonium chloride. The solution was then diluted with diethyl ether and washed with saturated sodium bicarbonate, brine, dried (MgSO4), filtered and concentrated. The crude mixture was then purified by silica gel flash column chromatography to afford 2-methyl-indan-2-carboxylic acid methyl ester (52 mg, 9%) as a white solid. 1H NMR (400 MHz, CDCl3) δ 7.16 (m, 4H), 3.72 (t, 3H), 3.48 (d, 2H), 2.81 (d, 2H), 1.36 (s, 3H). At −78° C warmed to 0° C. for 15 min −78° C. for an additional 15 min by stirring at −78° C. for 15 min, room temperature for 30 min quenched with saturated ammonium chloride The solution was then diluted with diethyl ether washed with saturated sodium bicarbonate, brine dried (MgSO4) filtered concentrated The crude mixture was then purified by silica gel flash column chromatography

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

Procedure: To a solution of methyl 2-methyl-2,3-dihydro-1H-indene-2-carboxylate (1.80 g, 9.46 mmol) in THF/water/MeOH (4/1/1 mL respectively) was added lithium hydroxide monohydrate (1.19 g, 28.4 mmol). The reaction mixture stirred at ambient temperature 4 h, acidified to pH 3 with 1 N HCl and extracted with Et2O (2×25 mL). Combined organics were washed (water, brine), dried over Na2SO4 and concentrated in vacuo affording the title compound as a white solid. 1H NMR (400 MHz, CDCl3) δ ppm 1.39 (s, 3H), 2.83 (d, J=15.9 Hz, 2 H), 3.50 (d, J=15.9 Hz, 2 H), 7.12-7.23 (m, 4H). extracted with Et2O (2×25 mL) Combined organics were washed (water, 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: Indane-2-carboxylic acid methyl ester (550 mg, 3.125 mmol) was dissolved in THF (20 mL). At −78° C. LiHMDS (1M solution in THF, 3.75 mL) was added into the reaction mixture. The solution was stirred for 15 min at −78° C., warmed to 0° C. for 15 min and then −78° C. for an additional 15 min. Methyl iodide (250 μL, 4.01 mmol) was then added into the reaction mixture followed by stirring at −78° C. for 15 min, room temperature for 30 min and then quenched with saturated ammonium chloride. The solution was then diluted with diethyl ether and washed with saturated sodium bicarbonate, brine, dried (MgSO4), filtered and concentrated. The crude mixture was then purified by silica gel flash column chromatography to afford 2-methyl-indan-2-carboxylic acid methyl ester (52 mg, 9%) as a white solid. 1H NMR (400 MHz, CDCl3) 7.16 (m, 4H), 3.72 (t, 3H), 3.48 (d, 2H), 2.81 (d, 2H), 1.36 (s, 3H). At −78° C warmed to 0° C. for 15 min −78° C. for an additional 15 min by stirring at −78° C. for 15 min, room temperature for 30 min quenched with saturated ammonium chloride The solution was then diluted with diethyl ether washed with saturated sodium bicarbonate, brine dried (MgSO4) filtered concentrated The crude mixture was then purified by silica gel flash column chromatography