2,3-dihydro-1H-indole-2-carboxamide

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

Procedure: To a suspension of LiAlH4 (6.0 g, 0.157 mol) in THF (200 mL) was added dropwise a suspension of 2-carbamoylindoline (17.0 g, 0.105 mol) in THF (700 mL) over 50 min. The mixture was refluxed for 5 h and then LiAlH4 (6.0 g) was added further. The reflux was continued additionally for 6 h and the mixture was treated with 10% aqueous THF after being cooled with ice bath. Aqueous 1N NaOH was added and the mixture was extracted with a mixture of diethyl ether and THF. The organic layer was washed with water and brine, dried over magnesium sulfate, and concentrated to give 13.91 g of 2-aminomethylindoline (90%): 1H NMR (270 MHz, CDCl3) δ7.11 (dd, 1H, J=7, 1 Hz), 7.01 (dt, 1H, J=1, 7 Hz), 6.68 (dt, 1H, J=1, 7 Hz), 6.61 (d, 1H, J=7 Hz), 3.84 (m, 1H), 3.11 (dd, 1H, J=16, 9 Hz), 2.86 (dd, 1H, J=13, 5 Hz), 2.70 (m, 2H). was added dropwise The mixture was refluxed for 5 h after being cooled with ice bath the mixture was extracted with a mixture of diethyl ether and THF The organic layer was washed with water and brine dried over magnesium sulfate concentrated

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

Procedure: To a solution of 2-methoxycarbonylindoline (22.733 g, 0.128 mmol) in methanol (230 mL) was introduced gaseous NH3 at room temperature until the solution was saturated with NH3. The mixture was stirred for 6 h at room temperature. The precipitates formed were collected, washed with methanol, and dried in vacuo to give 17.78 g of 2-carbamoylindoline (85%): 1H NMR (270 MHz, CDCl3) δ7.30 (bs, 1H), 7.11 (bs, 1H), 7.01 (d, 1H, J=7 Hz), 6.93 (dt, 1H, J=1, 7 Hz), 6.56 (m, 2H), 5.87 (bs, 1H), 4.12 (dd, 1H, J=10, 8 Hz), 3.25 (dd, 1H, J=16, 10 Hz), 2.93 (dd, 1H, J=16, 8 Hz). The precipitates formed were collected washed with methanol dried in vacuo

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

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

Procedure: To a suspension of LiAlH4 (6.0 g, 0.157 mol) in THF (200 mL) was added dropwise a suspension of 2-carbamoylindoline (17.0 g, 0.105 mol) in THF (700 mL) over 50 min. The mixture was refluxed for 5 h and then LiAlH4 (6.0 g) was added further. The reflux was continued additionally for 6 h and the mixture was treated with 10% aqueous THF after being cooled with ice bath. Aqueous 1N NaOH was added and the mixture was extracted with a mixture of diethyl ether and THF. The organic layer was washed with water and brine, dried over magnesium sulfate, and concentrated to give 13.91 g of 2-aminomethylindoline (90%): 1H NMR (270 MHz, CDCl3) δ7.11 (dd, 1H, J=7, 1 Hz), 7.01 (dt, 1H, J=1, 7 Hz), 6.68 (dt, 1H, J=1, 7 Hz), 6.61 (d, 1H, J=7 Hz), 3.84 (m, 1H), 3.11 (dd, 1H, J=16, 9 Hz), 2.86 (dd, 1H, J=13, 5 Hz), 2.70 (m, 2H). was added dropwise The mixture was refluxed for 5 h after being cooled with ice bath the mixture was extracted with a mixture of diethyl ether and THF The organic layer was washed with water and brine dried over magnesium sulfate concentrated

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

Procedure: To a solution of 2-methoxycarbonylindoline (22.733 g, 0.128 mmol) in methanol (230 mL) was introduced gaseous NH3 at room temperature until the solution was saturated with NH3. The mixture was stirred for 6 h at room temperature. The precipitates formed were collected, washed with methanol, and dried in vacuo to give 17.78 g of 2-carbamoylindoline (85%): 1H NMR (270 MHz, CDCl3) δ7.30 (bs, 1H), 7.11 (bs, 1H), 7.01 (d, 1H, J=7 Hz), 6.93 (dt, 1H, J=1, 7 Hz), 6.56 (m, 2H), 5.87 (bs, 1H), 4.12 (dd, 1H, J=10, 8 Hz), 3.25 (dd, 1H, J=16, 10 Hz), 2.93 (dd, 1H, J=16, 8 Hz). The precipitates formed were collected washed with methanol dried in vacuo

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

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

Procedure: To a suspension of LiAlH4 (6.0 g, 0.157 mol) in THF (200 mL) was added dropwise a suspension of 2-carbamoylindoline (17.0 g, 0.105 mol) in THF (700 mL) over 50 min. The mixture was refluxed for 5 h and then LiAlH4 (6.0 g) was added further. The reflux was continued additionally for 6 h and the mixture was treated with 10% aqueous THF after being cooled with ice bath. Aqueous 1N NaOH was added and the mixture was extracted with a mixture of diethyl ether and THF. The organic layer was washed with water and brine, dried over magnesium sulfate, and concentrated to give 13.91 g of 2-aminomethylindoline (90%): 1H NMR (270 MHz, CDCl3) δ7.11 (dd, 1H, J=7, 1 Hz), 7.01 (dt, 1H, J=1, 7 Hz), 6.68 (dt, 1H, J=1, 7 Hz), 6.61 (d, 1H, J=7 Hz), 3.84 (m, 1H), 3.11 (dd, 1H, J=16, 9 Hz), 2.86 (dd, 1H, J=13, 5 Hz), 2.70 (m, 2H). was added dropwise The mixture was refluxed for 5 h after being cooled with ice bath the mixture was extracted with a mixture of diethyl ether and THF The organic layer was washed with water and brine dried over magnesium sulfate concentrated

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

Procedure: To a solution of 2-methoxycarbonylindoline (22.733 g, 0.128 mmol) in methanol (230 mL) was introduced gaseous NH3 at room temperature until the solution was saturated with NH3. The mixture was stirred for 6 h at room temperature. The precipitates formed were collected, washed with methanol, and dried in vacuo to give 17.78 g of 2-carbamoylindoline (85%): 1H NMR (270 MHz, CDCl3) δ7.30 (bs, 1H), 7.11 (bs, 1H), 7.01 (d, 1H, J=7 Hz), 6.93 (dt, 1H, J=1, 7 Hz), 6.56 (m, 2H), 5.87 (bs, 1H), 4.12 (dd, 1H, J=10, 8 Hz), 3.25 (dd, 1H, J=16, 10 Hz), 2.93 (dd, 1H, J=16, 8 Hz). The precipitates formed were collected washed with methanol dried in vacuo

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

Procedure: LAH (20 mL, 1M solution in THF) was added dropwise through a syringe to a solution of (±)-indoline-2-carboxamide (2.2 g, 13.6 mmol) in anhydrous THF (20 mL) with cooling, and the resulting solution was refluxed under argon for 5 h. More LAH (20 mL) was added, and reflux was continued for another 6 h. 10% aqueous THF was added dropwise with cooling to destroy excess LAH, and then Et2O was added. After stirring for 10 min, the colorless precipitate was removed by filtration and washed with THF. The filtrate was dried (K2CO3), concentrated, and purified by silica gel flash chromatography (90:10:0.2 CH2Cl2 /MeOH/Et3N). The title compound (1.02 g, 51%) was obtained as an amber oil: MS (ES) m/e 149.0 (M+H)+. with cooling the resulting solution was refluxed under argon for 5 h reflux with cooling to destroy excess LAH Et2O was added the colorless precipitate was removed by filtration washed with THF The filtrate was dried (K2CO3) concentrated purified by silica gel flash chromatography (90:10:0.2 CH2Cl2 /MeOH/Et3N)

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

Procedure: Gaseous NH3 was bubbled into a solution of methyl (±)-indoline-2-carboxylate (4.3 g, 24.2 mmol) in methanol (50 mL) at RT for 30 min. The reaction was stirred for 18 h, then was filtered to afford the title compound (3.35 g 85%) as a colorless solid: MS (ES) m/e 163.0 (M+H)+. was filtered