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

Conditions: temp:50.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 3.80 g of 3-oxo-indan-1-carboxylic acid methyl ester (20.0 mmol, 1 equivalent) in 6 mL of toluene and 2 mL of acetonitrile was added 192 mg of zinc iodide (0.600 mmol, 0.03 equivalent) followed by 3.47 mL of trimethylsilyl cyanide (26.0 mmol, 1.3 equivalent). The reaction mixture was heated to 50° C. for 5 hours. The reaction mixture was then cooled to room temperature and diluted with 12 mL of toluene and 8 mL of a saturated aqueous sodium bicarbonate solution. After stirring the mixture for 1 hour the layers were separated. The organic layer was washed with another 8 mL of a saturated aqueous sodium bicarbonate solution followed by 8 mL of a saturated aqueous sodium chloride solution. The organic layer was dried over anhydrous sodium sulfate and concentrated in vacuo to give 3-cyano-3-trimethylsilanyloxy-indan-1-carboxylic acid methyl ester as an oil (5.61 g, 97%). The silylated cyanohydrin title compound was obtained as a mixture of two diastereomers in a 2:1 ratio: 1H NMR (400 MHz, CDCl3): (major isomer) δ 7.54-7.50 (m, 1H), 7.42-7.38 (m, 3H), 4.14 (t, J=7.7 Hz, 1H), 3.78 (s, 3H), 3.01 (dd, J=13.3, 7.5 Hz, 1H), 2.79 (dd, J=13.3, 7.5 Hz, 1H), 0.26 (s, 9H); (minor isomer) δ 7.59-7.55 (m, 1H), 7.48-7.44 (m, 3H), 4.29 (t, J =7.5 Hz, 1H), 3.78 (s, 3H), 3.03 (dd, J=13.7, 7.5 Hz, 1H), 2.70 (dd, J=13.7, 7.5 Hz, 1H), 0.14 (s, 9H); 13C NMR (100 MHz, CDCl3): (unassigned) δ 172,3, 172.0, 142,3, 142.1, 140.1, 138.8, 130.8, 130.5, 129.1, 128.9, 125.8, 125.6, 124.7, 124.3, 120.8, 120.6, 75.4, 75.3, 52.7, 52.7, 47.4, 46.8, 45.6, 45.3, 1,4, 1.3; IR (neat, cm−1): 2956, 1739, 1477, 1436, 1253, 1197, 1169, 1135, 1092, 1033, 1011, 880, 843, 756, 623; Anal. Calcd for C15H119NO3Si: C, 62,25; H, 6.62; N, 4.84; Found: C, 62,20; H, 6.53; N, 4.92. The reaction mixture was then cooled to room temperature were separated The organic layer was washed with another 8 mL of a saturated aqueous sodium bicarbonate solution The organic layer was dried over anhydrous sodium sulfate concentrated in vacuo

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

Procedure: A solution of 10.0 g of 3-oxo-indan-1-carboxylic acid (56.8 mmol, 1.0 equivalent) and 0.25 mL of concentrated sulfuric acid in 20 mL of methanol was heated to a reflux for 4 hours. The reaction mixture was then cooled to room temperature and diluted with 100 mL of methyl-tert-butyl alcohol. The organic solution was washed twice with 60 mL of a saturated aqueous sodium bicarbonate solution, and once with 50 mL of a saturated aqueous sodium chloride solution. The organic layer was dried over anhydrous sodium sulfate and concentrated. The title compound crystallized as a white solid upon concentration, (10.4 g, 96%); mp: 46-47° C.; 1H NMR (400 MHz, CDCl3): δ 7.74 (d, J=7.6 Hz, 1H), 7.68 (d, J=7.6 Hz, 1H), 7.62 (t, J=7.6 Hz, 1H), 7.44 (t, J=7.6 Hz, 1H), 4.29 (dd, J=8.0, 3.4 Hz, 1H), 3.76 (s, 3H), 3.13 (dd, J=19.1, 3.4 Hz, 1H), 2.86 (dd, J=19.1, 8.0 Hz, 1H); 13C NMR (100 MHz, CD3OD): δ 204.4, 172.5, 151.3, 136.5, 135.2, 129.1, 126.7, 124.1, 52.9, 43.8, 39.7; IR (neat, cm−1): 2954, 1710, 1602, 1462, 1435, 1403, 1319, 1241, 1206, 1168, 1092, 1044, 1014, 986, 881, 837, 760, 686, 580, 538. a reflux for 4 hours The organic solution was washed twice with 60 mL of a saturated aqueous sodium bicarbonate solution The organic layer was dried over anhydrous sodium sulfate concentrated The title compound crystallized as a white solid upon concentration, (10.4 g, 96%)

Conditions: temp:50.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 3.80 g of 3-oxo-indan-1-carboxylic acid methyl ester (20.0 mmol, 1 equivalent) in 6 mL of toluene and 2 mL of acetonitrile was added 192 mg of zinc iodide (0.600 mmol, 0.03 equivalent) followed by 3.47 mL of trimethylsilyl cyanide (26.0 mmol, 1.3 equivalent). The reaction mixture was heated to 50° C. for 5 hours. The reaction mixture was then cooled to room temperature and diluted with 12 mL of toluene and 8 mL of a saturated aqueous sodium bicarbonate solution. After stirring the mixture for 1 hour the layers were separated. The organic layer was washed with another 8 mL of a saturated aqueous sodium bicarbonate solution followed by 8 mL of a saturated aqueous sodium chloride solution. The organic layer was dried over anhydrous sodium sulfate and concentrated in vacuo to give 3-cyano-3-trimethylsilanyloxy-indan-1-carboxylic acid methyl ester as an oil (5.61 g, 97%). The silylated cyanohydrin title compound was obtained as a mixture of two diastereomers in a 2:1 ratio: 1H NMR (400 MHz, CDCl3): (major isomer) δ 7.54–7.50 (m, 1H), 7.42–7.38 (m, 3H), 4.14 (t, J=7.7 Hz, 1H), 3.78 (s, 3H), 3.01 (dd, J=13.3, 7.5 Hz, 1H), 2.79 (dd, J=13.3, 7.5 Hz, 1H), 0.26 (s, 9H); (minor isomer) 67.59–7.55 (m, 1H), 7.48–7.44 (m, 3H), 4.29 (t, J=7.5 Hz, 1H), 3.78 (s, 3H), 3.03 (dd, J=13.7, 7.5 Hz, 1H), 2.70 (dd, J=13.7, 7.5 Hz, 1H), 0.14 (s, 9H); 13C NMR (100 MHz, CDCl3): (unassigned) δ 172.3, 172.0, 142.3, 142.1, 140.1, 138.8, 130.8, 130.5, 129.1, 128.9, 125.8, 125.6, 124.7, 124.3, 120.8, 120.6, 75.4, 75.3, 52.7, 52.7, 47.4, 46.8, 45.6, 45.3, 1.4, 1.3; IR (neat, cm−1): 2956, 1739, 1477, 1436, 1253, 1197, 1169, 1135, 1092, 1033, 1011, 880, 843, 756, 623; Anal. Calcd for C15H19NO3Si: C, 62.25; H, 6.62; N, 4.84; Found: C, 62.20; H, 6.53; N, 4.92. The reaction mixture was then cooled to room temperature were separated The organic layer was washed with another 8 mL of a saturated aqueous sodium bicarbonate solution The organic layer was dried over anhydrous sodium sulfate concentrated in vacuo

Conditions: temp:50.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 3.80 g of 3-oxo-indan-1-carboxylic acid methyl ester (20.0 mmol, 1 equivalent) in 6 mL of toluene and 2 mL of acetonitrile was added 192 mg of zinc iodide (0.600 mmol, 0.03 equivalent) followed by 3.47 mL of trimethylsilyl cyanide (26.0 mmol, 1.3 equivalent). The reaction mixture was heated to 50° C. for 5 hours. The reaction mixture was then cooled to room temperature and diluted with 12 mL of toluene and 8 mL of a saturated aqueous sodium bicarbonate solution. After stirring the mixture for 1 hour the layers were separated. The organic layer was washed with another 8 mL of a saturated aqueous sodium bicarbonate solution followed by 8 mL of a saturated aqueous sodium chloride solution. The organic layer was dried over anhydrous sodium sulfate and concentrated in vacuo to give 3-cyano-3-trimethylsilanyloxy-indan-1-carboxylic acid methyl ester as an oil (5.61 g, 97%). The silylated cyanohydrin title compound was obtained as a mixture of two diastereomers in a 2:1 ratio: 1H NMR (400 MHz, CDCl3): (major isomer) δ 7.54–7.50 (m, 1H), 7.42–7.38 (m, 3H), 4.14 (t, J=7.7 Hz, 1H), 3.78 (s, 3H), 3.01 (dd, J=13.3, 7.5 Hz, 1H), 2.79 (dd, J=13.3, 7.5 Hz, 1H), 0.26 (s, 9H); (minor isomer) 67.59–7.55 (m, 1H), 7.48–7.44 (m, 3H), 4.29 (t, J=7.5 Hz, 1H), 3.78 (s, 3H), 3.03 (dd, J=13.7, 7.5 Hz, 1H), 2.70 (dd, J=13.7, 7.5 Hz, 1H), 0.14 (s, 9H); 13C NMR (100 MHz, CDCl3): (unassigned) δ 172.3, 172.0, 142.3, 142.1, 140.1, 138.8, 130.8, 130.5, 129.1, 128.9, 125.8, 125.6, 124.7, 124.3, 120.8, 120.6, 75.4, 75.3, 52.7, 52.7, 47.4, 46.8, 45.6, 45.3, 1.4, 1.3; IR (neat, cm−1): 2956, 1739, 1477, 1436, 1253, 1197, 1169, 1135, 1092, 1033, 1011, 880, 843, 756, 623; Anal. Calcd for C15H19NO3Si: C, 62.25; H, 6.62; N, 4.84; Found: C, 62.20; H, 6.53; N, 4.92. The reaction mixture was then cooled to room temperature were separated The organic layer was washed with another 8 mL of a saturated aqueous sodium bicarbonate solution The organic layer was dried over anhydrous sodium sulfate concentrated in vacuo

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

Procedure: A solution of 10.0 g of 3-oxo-indan-1-carboxylic acid (56.8 mmol, 1.0 equivalent) and 0.25 mL of concentrated sulfuric acid in 20 mL of methanol was heated to a reflux for 4 hours. The reaction mixture was then cooled to room temperature and diluted with 100 mL of methyl-tert-butyl alcohol. The organic solution was washed twice with 60 mL of a saturated aqueous sodium bicarbonate solution, and once with 50 mL of a saturated aqueous sodium chloride solution. The organic layer was dried over anhydrous sodium sulfate and concentrated. The title compound crystallized as a white solid upon concentration, (10.4 g, 96%); mp: 46–47° C.; 1H NMR (400 MHz, CDCl3): δ 7.74 (d, J=7.6 Hz, 1H), 7.68 (d, J=7.6 Hz, 1H), 7.62 (t, J=7.6 Hz, 1H), 7.44 (t, J=7.6 Hz, 1H), 4.29 (dd, J=8.0, 3.4 Hz, 1H), 3.76 (s, 3H), 3.13 (dd, J=19.1, 3.4 Hz, 1H), 2.86 (dd, J=19.1, 8.0 Hz, 1H); 13C NMR (100 MHz, CD3OD): δ 204.4, 172.5, 151.3, 136.5, 135.2, 129.1, 126.7, 124.1, 52.9, 43.8, 39.7; IR (neat, cm−1): 2954, 1710, 1602, 1462, 1435, 1403, 1319, 1241, 1206, 1168, 1092, 1044, 1014, 986, 881, 837, 760, 686, 580, 538. a reflux for 4 hours The organic solution was washed twice with 60 mL of a saturated aqueous sodium bicarbonate solution The organic layer was dried over anhydrous sodium sulfate concentrated The title compound crystallized as a white solid upon concentration, (10.4 g, 96%)

Conditions: temp:50.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 3.80 g of 3-oxo-indan-1-carboxylic acid methyl ester (20.0 mmol, 1 equivalent) in 6 mL of toluene and 2 mL of acetonitrile was added 192 mg of zinc iodide (0.600 mmol, 0.03 equivalent) followed by 3.47 mL of trimethylsilyl cyanide (26.0 mmol, 1.3 equivalent). The reaction mixture was heated to 50° C. for 5 hours. The reaction mixture was then cooled to room temperature and diluted with 12 mL of toluene and 8 mL of a saturated aqueous sodium bicarbonate solution. After stirring the mixture for 1 hour the layers were separated. The organic layer was washed with another 8 mL of a saturated aqueous sodium bicarbonate solution followed by 8 mL of a saturated aqueous sodium chloride solution. The organic layer was dried over anhydrous sodium sulfate and concentrated in vacuo to give 3-cyano-3-trimethylsilanyloxy-indan-1-carboxylic acid methyl ester as an oil (5.61 g, 97%). The silylated cyanohydrin title compound was obtained as a mixture of two diastereomers in a 2:1 ratio: 1H NMR (400 MHz, CDCl3): (major isomer) δ 7.54-7.50 (m, 1H), 7.42-7.38 (m, 3H), 4.14 (t, J=7.7 Hz, 1H), 3.78 (s, 3H), 3.01 (dd, J=13.3, 7.5 Hz, 1H), 2.79 (dd, J=13.3, 7.5 Hz, 1H), 0.26 (s, 9H); (minor isomer) δ 7.59-7.55 (m, 1H), 7.48-7.44 (m, 3H), 4.29 (t, J =7.5 Hz, 1H), 3.78 (s, 3H), 3.03 (dd, J=13.7, 7.5 Hz, 1H), 2.70 (dd, J=13.7, 7.5 Hz, 1H), 0.14 (s, 9H); 13C NMR (100 MHz, CDCl3): (unassigned) δ 172,3, 172.0, 142,3, 142.1, 140.1, 138.8, 130.8, 130.5, 129.1, 128.9, 125.8, 125.6, 124.7, 124.3, 120.8, 120.6, 75.4, 75.3, 52.7, 52.7, 47.4, 46.8, 45.6, 45.3, 1,4, 1.3; IR (neat, cm−1): 2956, 1739, 1477, 1436, 1253, 1197, 1169, 1135, 1092, 1033, 1011, 880, 843, 756, 623; Anal. Calcd for C15H119NO3Si: C, 62,25; H, 6.62; N, 4.84; Found: C, 62,20; H, 6.53; N, 4.92. The reaction mixture was then cooled to room temperature were separated The organic layer was washed with another 8 mL of a saturated aqueous sodium bicarbonate solution The organic layer was dried over anhydrous sodium sulfate concentrated in vacuo

Conditions: temp:50.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 3.80 g of 3-oxo-indan-1-carboxylic acid methyl ester (20.0 mmol, 1 equivalent) in 6 mL of toluene and 2 mL of acetonitrile was added 192 mg of zinc iodide (0.600 mmol, 0.03 equivalent) followed by 3.47 mL of trimethylsilyl cyanide (26.0 mmol, 1.3 equivalent). The reaction mixture was heated to 50° C. for 5 hours. The reaction mixture was then cooled to room temperature and diluted with 12 mL of toluene and 8 mL of a saturated aqueous sodium bicarbonate solution. After stirring the mixture for 1 hour the layers were separated. The organic layer was washed with another 8 mL of a saturated aqueous sodium bicarbonate solution followed by 8 mL of a saturated aqueous sodium chloride solution. The organic layer was dried over anhydrous sodium sulfate and concentrated in vacuo to give 3-cyano-3-trimethylsilanyloxy-indan-1-carboxylic acid methyl ester as an oil (5.61 g, 97%). The silylated cyanohydrin title compound was obtained as a mixture of two diastereomers in a 2:1 ratio: 1H NMR (400 MHz, CDCl3): (major isomer) δ 7.54-7.50 (m, 1H), 7.42-7.38 (m, 3H), 4.14 (t, J=7.7 Hz, 1H), 3.78 (s, 3H), 3.01 (dd, J=13.3, 7.5 Hz, 1H), 2.79 (dd, J=13.3, 7.5 Hz, 1H), 0.26 (s, 9H); (minor isomer) δ 7.59-7.55 (m, 1H), 7.48-7.44 (m, 3H), 4.29 (t, J =7.5 Hz, 1H), 3.78 (s, 3H), 3.03 (dd, J=13.7, 7.5 Hz, 1H), 2.70 (dd, J=13.7, 7.5 Hz, 1H), 0.14 (s, 9H); 13C NMR (100 MHz, CDCl3): (unassigned) δ 172,3, 172.0, 142,3, 142.1, 140.1, 138.8, 130.8, 130.5, 129.1, 128.9, 125.8, 125.6, 124.7, 124.3, 120.8, 120.6, 75.4, 75.3, 52.7, 52.7, 47.4, 46.8, 45.6, 45.3, 1,4, 1.3; IR (neat, cm−1): 2956, 1739, 1477, 1436, 1253, 1197, 1169, 1135, 1092, 1033, 1011, 880, 843, 756, 623; Anal. Calcd for C15H119NO3Si: C, 62,25; H, 6.62; N, 4.84; Found: C, 62,20; H, 6.53; N, 4.92. The reaction mixture was then cooled to room temperature were separated The organic layer was washed with another 8 mL of a saturated aqueous sodium bicarbonate solution The organic layer was dried over anhydrous sodium sulfate concentrated in vacuo

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

Procedure: A solution of 10.0 g of 3-oxo-indan-1-carboxylic acid (56.8 mmol, 1.0 equivalent) and 0.25 mL of concentrated sulfuric acid in 20 mL of methanol was heated to a reflux for 4 hours. The reaction mixture was then cooled to room temperature and diluted with 100 mL of methyl-tert-butyl alcohol. The organic solution was washed twice with 60 mL of a saturated aqueous sodium bicarbonate solution, and once with 50 mL of a saturated aqueous sodium chloride solution. The organic layer was dried over anhydrous sodium sulfate and concentrated. The title compound crystallized as a white solid upon concentration, (10.4 g, 96%); mp: 46-47° C.; 1H NMR (400 MHz, CDCl3): δ 7.74 (d, J=7.6 Hz, 1H), 7.68 (d, J=7.6 Hz, 1H), 7.62 (t, J=7.6 Hz, 1H), 7.44 (t, J=7.6 Hz, 1H), 4.29 (dd, J=8.0, 3.4 Hz, 1H), 3.76 (s, 3H), 3.13 (dd, J=19.1, 3.4 Hz, 1H), 2.86 (dd, J=19.1, 8.0 Hz, 1H); 13C NMR (100 MHz, CD3OD): δ 204.4, 172.5, 151.3, 136.5, 135.2, 129.1, 126.7, 124.1, 52.9, 43.8, 39.7; IR (neat, cm−1): 2954, 1710, 1602, 1462, 1435, 1403, 1319, 1241, 1206, 1168, 1092, 1044, 1014, 986, 881, 837, 760, 686, 580, 538. a reflux for 4 hours The organic solution was washed twice with 60 mL of a saturated aqueous sodium bicarbonate solution The organic layer was dried over anhydrous sodium sulfate concentrated The title compound crystallized as a white solid upon concentration, (10.4 g, 96%)

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

Procedure: To a solution of 1 g of methyl 3-oxoindane-1-carboxylate in 10 ml of toluene were added 0.78 ml of (1S)-1-(4-methoxyphenyl)ethanamine and 100 mg of p-toluenesulfonic acid monohydrate, followed by heating to reflux for 5 hours using a Dean-Stark type reflux device. Then, 634 mg of magnesium sulfate was added thereto, followed by heating to reflux for 5 hours using a Dean-Stark type reflux device. Further, 634 mg of magnesium sulfate was added thereto, followed by heating to reflux for 5 hours using a Dean-Stark type reflux device. The insoluble material was removed by filtration and the solvent was then evaporated under reduced pressure to obtain an intermediate product. To a solution of the obtained intermediate product in 17 ml of ethanol was added 209 mg of sodium borohydride under ice-cooling, followed by stirring for 1 hour under ice-cooling. The solvent was evaporated under reduced pressure, and to the obtained residue were added water, a saturated aqueous sodium hydrogen carbonate solution, and ethyl acetate to carry out a layer separation operation. The organic layer was washed with water and saturated brine, and dried over anhydrous magnesium sulfate, and the solvent was evaporated under reduced pressure. The obtained residue was purified by silica gel column chromatography to obtain 1.195 g of methyl (3S)-3-{[(1S)-1-(4-methoxyphenyl)ethyl]amino}indane-1-carboxylate. by heating to reflux for 5 hours reflux device by heating to reflux for 5 hours reflux device by heating to reflux for 5 hours reflux device The insoluble material was removed by filtration the solvent was then evaporated under reduced pressure to obtain an intermediate product cooling cooling The solvent was evaporated under reduced pressure to the obtained residue were added water a layer separation operation The organic layer was washed with water and saturated brine dried over anhydrous magnesium sulfate the solvent was evaporated under reduced pressure The obtained residue was purified by silica gel column chromatography

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

Procedure: To a solution of 1 g of methyl 3-oxoindane-1-carboxylate in 10 ml of toluene were added 0.78 ml of (1S)-1-(4-methoxyphenyl)ethanamine and 100 mg of p-toluenesulfonic acid monohydrate, followed by heating to reflux for 5 hours using a Dean-Stark type reflux device. Then, 634 mg of magnesium sulfate was added thereto, followed by heating to reflux for 5 hours using a Dean-Stark type reflux device. Further, 634 mg of magnesium sulfate was added thereto, followed by heating to reflux for 5 hours using a Dean-Stark type reflux device. The insoluble material was removed by filtration and the solvent was then evaporated under reduced pressure to obtain an intermediate product. To a solution of the obtained intermediate product in 17 ml of ethanol was added 209 mg of sodium borohydride under ice-cooling, followed by stirring for 1 hour under ice-cooling. The solvent was evaporated under reduced pressure, and to the obtained residue were added water, a saturated aqueous sodium hydrogen carbonate solution, and ethyl acetate to carry out a layer separation operation. The organic layer was washed with water and saturated brine, and dried over anhydrous magnesium sulfate, and the solvent was evaporated under reduced pressure. The obtained residue was purified by silica gel column chromatography to obtain 1.195 g of methyl (3S)-3-{[(1S)-1-(4-methoxyphenyl)ethyl]amino}indane-1-carboxylate. by heating to reflux for 5 hours reflux device by heating to reflux for 5 hours reflux device by heating to reflux for 5 hours reflux device The insoluble material was removed by filtration the solvent was then evaporated under reduced pressure to obtain an intermediate product cooling cooling The solvent was evaporated under reduced pressure to the obtained residue were added water a layer separation operation The organic layer was washed with water and saturated brine dried over anhydrous magnesium sulfate the solvent was evaporated under reduced pressure The obtained residue was purified by silica gel column chromatography

Conditions: temp:50.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 3.80 g of 3-oxo-indan-1-carboxylic acid methyl ester (20.0 mmol, 1 equivalent) in 6 mL of toluene and 2 mL of acetonitrile was added 192 mg of zinc iodide (0.600 mmol, 0.03 equivalent) followed by 3.47 mL of trimethylsilyl cyanide (26.0 mmol, 1.3 equivalent). The reaction mixture was heated to 50° C. for 5 hours. The reaction mixture was then cooled to room temperature and diluted with 12 mL of toluene and 8 mL of a saturated aqueous sodium bicarbonate solution. After stirring the mixture for 1 hour the layers were separated. The organic layer was washed with another 8 mL of a saturated aqueous sodium bicarbonate solution followed by 8 mL of a saturated aqueous sodium chloride solution. The organic layer was dried over anhydrous sodium sulfate and concentrated in vacuo to give 3-cyano-3-trimethylsilanyloxy-indan-1-carboxylic acid methyl ester as an oil (5.61 g, 97%). The silylated cyanohydrin title compound was obtained as a mixture of two diastereomers in a 2:1 ratio: 1H NMR (400 MHz, CDCl3): (major isomer) δ 7.54–7.50 (m, 1H), 7.42–7.38 (m, 3H), 4.14 (t, J=7.7 Hz, 1H), 3.78 (s, 3H), 3.01 (dd, J=13.3, 7.5 Hz, 1H), 2.79 (dd, J=13.3, 7.5 Hz, 1H), 0.26 (s, 9H); (minor isomer) 67.59–7.55 (m, 1H), 7.48–7.44 (m, 3H), 4.29 (t, J=7.5 Hz, 1H), 3.78 (s, 3H), 3.03 (dd, J=13.7, 7.5 Hz, 1H), 2.70 (dd, J=13.7, 7.5 Hz, 1H), 0.14 (s, 9H); 13C NMR (100 MHz, CDCl3): (unassigned) δ 172.3, 172.0, 142.3, 142.1, 140.1, 138.8, 130.8, 130.5, 129.1, 128.9, 125.8, 125.6, 124.7, 124.3, 120.8, 120.6, 75.4, 75.3, 52.7, 52.7, 47.4, 46.8, 45.6, 45.3, 1.4, 1.3; IR (neat, cm−1): 2956, 1739, 1477, 1436, 1253, 1197, 1169, 1135, 1092, 1033, 1011, 880, 843, 756, 623; Anal. Calcd for C15H119NO3Si: C, 62.25; H, 6.62; N, 4.84; Found: C, 62.20; H, 6.53; N, 4.92. The reaction mixture was then cooled to room temperature were separated The organic layer was washed with another 8 mL of a saturated aqueous sodium bicarbonate solution The organic layer was dried over anhydrous sodium sulfate concentrated in vacuo

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

Procedure: A solution of 10.0 g of 3-oxo-indan-1-carboxylic acid (56.8 mmol, 1.0 equivalent) and 0.25 mL of concentrated sulfuric acid in 20 mL of methanol was heated to a reflux for 4 hours. The reaction mixture was then cooled to room temperature and diluted with 100 mL of methyl-tert-butyl alcohol. The organic solution was washed twice with 60 mL of a saturated aqueous sodium bicarbonate solution, and once with 50 mL of a saturated aqueous sodium chloride solution. The organic layer was dried over anhydrous sodium sulfate and concentrated. The title compound crystallized as a white solid upon concentration, (10.4 g, 96%); mp: 46–47° C.; 1H NMR (400 MHz, CDCl3): δ 7.74 (d, J=7.6 Hz, 1H), 7.68 (d, J=7.6 Hz, 1H), 7.62 (t, J=7.6 Hz, 1H), 7.44 (t, J=7.6 Hz, 1H), 4.29 (dd, J=8.0, 3.4 Hz, 1H), 3.76 (s, 3H), 3.13 (dd, J=19.1, 3.4 Hz, 1H), 2.86 (dd, J=19.1, 8.0 Hz, 1H); 13C NMR (100 MHz, CD3OD): δ 204.4, 172.5, 151.3, 136.5, 135.2, 129.1, 126.7, 124.1, 52.9, 43.8, 39.7; IR (neat, cm−1): 2954, 1710, 1602, 1462, 1435, 1403, 1319, 1241, 1206, 1168, 1092, 1044, 1014,986, 881, 837, 760, 686, 580, 538. a reflux for 4 hours The organic solution was washed twice with 60 mL of a saturated aqueous sodium bicarbonate solution The organic layer was dried over anhydrous sodium sulfate concentrated The title compound crystallized as a white solid upon concentration, (10.4 g, 96%)