2-methyl-1-phenylpropan-1-amine

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

Procedure: In air, 2-pyridinecarboxaldehyde (0.185 g, 0.164 mL, 1.72 mmol, 1.00 equiv) was added to a solution of 2-methyl-1-phenylpropan-1-amine (0.257 g, 1.72 mmol, 1.00 equiv) in CH2Cl2 (8 mL). After heating at reflux for 2 h with azeotropic removal of water using a Dean-Stark trap, the reaction mixture was concentrated under reduced pressure and dried under high vacuum to give ligand (L-1), (E)-2-Methyl-1-phenyl-N-(pyridin-2-ylmethylene)propan-1-amine, as a yellow oil (0.379 g, 92% yield). After heating the reaction mixture was concentrated under reduced pressure dried under high vacuum

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

Procedure: In air, 2-pyridinecarboxaldehyde (0.185 g, 0.164 mL, 1.72 mmol, 1.00 equiv) was added to a solution of 2-methyl-1-phenylpropan-1-amine (0.257 g, 1.72 mmol, 1.00 equiv) in CH2Cl2 (8 mL). After heating at reflux for 2 h with azeotropic removal of water using a Dean-Stark trap, the reaction mixture was concentrated under reduced pressure and dried under high vacuum to give ligand (L-1), (E)-2-Methyl-1-phenyl-N-(pyridin-2-ylmethylene)propan-1-amine, as a yellow oil (0.379 g, 92% yield). After heating the reaction mixture was concentrated under reduced pressure dried under high vacuum

Conditions: temp:60.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To 2-methoxy-N-(2-methyl-1-phenylpropyl)aniline (1.36 g, 5.34 mmol, 1.00 equiv) in 2:1 v/v MeCN/H2O (76 mL) was added AgNO3 (0.271 g, 1.60 mmol, 0.300 equiv) and the reaction mixture was heated to 60° C. Ammonium persulfate (8.58 g, 37.6 mmol, 7.04 equiv) was added in three portions over 15 min and the reaction mixture was heated at 60° C. for 1 h. An aqueous solution of HCl (10 mL, 2 N in H2O) was added. The reaction mixture was filtered through a celite pad, eluting with H2O. The aqueous layer was washed with Et2O (3×30 mL) and the combined organic layers were washed with HCl (2×30 mL, 0.5 N in H2O). The combined aqueous layers were basified with 2.5 M NaOH and the aqueous layer was extracted with Et2O (4×20 mL). The combined organic layers were washed with brine, dried over MgSO4, filtered, and concentrated. The residue was purified by Kugelrohr distillation (50 mTorr, 60° C.) to give 2-methyl-1-phenylpropan-1-amine as a colorless oil (0.257 g, 32% yield). the reaction mixture was heated at 60° C. for 1 h The reaction mixture was filtered through a celite pad eluting with H2O The aqueous layer was washed with Et2O (3×30 mL) the combined organic layers were washed with HCl (2×30 mL, 0.5 N in H2O) the aqueous layer was extracted with Et2O (4×20 mL) The combined organic layers were washed with brine dried over MgSO4 filtered concentrated The residue was purified by Kugelrohr distillation (50 mTorr, 60° C.)

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

Procedure: A solution of isobutyrophenone (5.1 mL, 33.7 mmol) and formic acid (1.3 mL, 33.7 mmol) in formamide was stirred at 165-180° C. for 20 h. The mixture was cooled, diluted with water, and extracted with benzene. The benzene was concentrated down and the residue was boiled in 3 M HCl (10 mL) for 48 h. The cooled reaction mixture was added to diethyl ether and extracted with water. The combined water extracts were basified with 20% NaOH, and extracted with dichloromethane. The combined extracts were washed with brine, dried (Na2SO4) and concentrated in vacuo to yield 3.09 g (61%) of the desired amine: 1H NMR (400 MHz, CD3OD): δ 7.33-7.23 (m, 4H), 7.22-7.20 (m, 1H), 3.49 (d, 1H), 1.87 (m, 1H), 1.00 (d, 3H), 0.73 (d, 3H). MS (ESI) m/z: Calculated: 149.12; Observed: 149.9 (M++1). The mixture was cooled extracted with benzene The benzene was concentrated down The cooled reaction mixture extracted with water extracted with dichloromethane The combined extracts were washed with brine dried (Na2SO4) concentrated in vacuo

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

Procedure: A solution of isobutyrophenone (5.1 mL, 33.7 mmol) and formic acid (1.3 mL, 33.7 mmol) in formamide was stirred at 165-180° C. for 20 h. The mixture was cooled, diluted with water, and extracted with benzene. The benzene was concentrated down and the residue was boiled in 3 M HCl (10 mL) for 48 h. The cooled reaction mixture was added to diethyl ether and extracted with water. The combined water extracts were basified with 20% NaOH, and extracted with dichloromethane. The combined extracts were washed with brine, dried (Na2SO4) and concentrated in vacuo to yield 3.09 g (61%) of the desired amine: 1H NMR (400 MHz, CD3OD): δ 7.33-7.23 (m, 4H), 7.22-7.20 (m, 1H), 3.49 (d, 1H), 1.87 (m, 1H), 1.00 (d, 3H), 0.73 (d, 3H). MS (ESI) m/z: Calculated: 149.12; Observed: 149.9 (M++1). The mixture was cooled extracted with benzene The benzene was concentrated down The cooled reaction mixture extracted with water extracted with dichloromethane The combined extracts were washed with brine dried (Na2SO4) concentrated in vacuo

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

Procedure: A solution of isobutyrophenone (5.1 mL, 33.7 mmol) and formic acid (1.3 mL, 33.7 mmol) in formamide was stirred at 165-180° C. for 20 h. The mixture was cooled, diluted with water, and extracted with benzene. The benzene was concentrated down and the residue was boiled in 3 M HCl (10 mL) for 48 h. The cooled reaction mixture was added to diethyl ether and extracted with water. The combined water extracts were basified with 20% NaOH, and extracted with dichloromethane. The combined extracts were washed with brine, dried (Na2SO4) and concentrated in vacuo to yield 3.09 g (61%) of the desired amine: 1H NMR (400 MHz, CD3OD): δ 7.33-7.23 (m, 4H), 7.22-7.20 (m, 1H), 3.49 (d, 1H), 1.87 (m, 1H), 1.00 (d, 3H), 0.73 (d, 3H). MS (ESI) m/z: Calculated: 149.12; Observed: 149.9 (M++1). The mixture was cooled extracted with benzene The benzene was concentrated down The cooled reaction mixture extracted with water extracted with dichloromethane The combined extracts were washed with brine dried (Na2SO4) concentrated in vacuo

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

Procedure: A solution of 2-methyl-1-phenylpropan-1-amine (1.0 g, 6.7 mmol), 2,4-difluoronitrobenzene (0.74 mL, 6.7 mmol) and N,N-diisopropylethylamine (2.3 mL, 13.4 mmol) in acetonitrile was stirred at room temperature for 32 h. The solvent was concentrated in vacuo, the residue was taken up in dichloromethane and washed with water, dried, and concentrated under reduced pressure to yield 1.79 g (93%) of the desired aniline: 1H NMR (400 MHz, CDCl3): δ 8.78 (br d, 1H), 8.21 (dd, 1H), 7.37-7.31 (m, 4H), 7.28-7.24 (m, 1H), 6.44-6.35 (m, 2H), 4.43 (t, 1H), 2.18 (m, 1H), 1.06 (d, 3H), 0.97 (d, 3H). The solvent was concentrated in vacuo washed with water dried concentrated under reduced pressure

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

Procedure: A solution of isobutyrophenone (5.1 mL, 33.7 mmol) and formic acid (1.3 mL, 33.7 mmol) in formamide was stirred at 165-180° C. for 20 h. The mixture was cooled, diluted with water, and extracted with benzene. The benzene was concentrated down and the residue was boiled in 3 M HCl (10 mL) for 48 h. The cooled reaction mixture was added to diethyl ether and extracted with water. The combined water extracts were basified with 20% NaOH, and extracted with dichloromethane. The combined extracts were washed with brine, dried (Na2SO4) and concentrated in vacuo to yield 3.09 g (61%) of the desired amine: 1H NMR (400 MHz, CD3OD): δ 7.33-7.23 (m, 4H), 7.22-7.20 (m, 1H), 3.49 (d, 1H), 1.87 (m, 1H), 1.00 (d, 3H), 0.73 (d, 3H). MS (ESI) m/z: Calculated: 149.12; Observed: 149.9 (M++1). The mixture was cooled extracted with benzene The benzene was concentrated down The cooled reaction mixture extracted with water extracted with dichloromethane The combined extracts were washed with brine dried (Na2SO4) concentrated in vacuo

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

Procedure: A solution of 2-methyl-1-phenylpropan-1-amine (1.0 g, 6.7 mmol), 2,4-difluoronitrobenzene (0.74 mL, 6.7 mmol) and N,N-diisopropylethylamine (2.3 mL, 13.4 mmol) in acetonitrile was stirred at room temperature for 32 h. The solvent was concentrated in vacuo, the residue was taken up in dichloromethane and washed with water, dried, and concentrated under reduced pressure to yield 1.79 g (93%) of the desired aniline: 1H NMR (400 MHz, CDCl3): δ 8.78 (br d, 1H), 8.21 (dd, 1H), 7.37-7.31 (m, 4H), 7.28-7.24 (m, 1H), 6.44-6.35 (m, 2H), 4.43 (t, 1H), 2.18 (m, 1H), 1.06 (d, 3H), 0.97 (d, 3H). The solvent was concentrated in vacuo washed with water dried concentrated under reduced pressure

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

Procedure: In air, 2-pyridinecarboxaldehyde (0.185 g, 0.164 mL, 1.72 mmol, 1.00 equiv) was added to a solution of 2-methyl-1-phenylpropan-1-amine (0.257 g, 1.72 mmol, 1.00 equiv) in CH2Cl2 (8 mL). After heating at reflux for 2 h with azeotropic removal of water using a Dean-Stark trap, the reaction mixture was concentrated under reduced pressure and dried under high vacuum to give ligand (L-1), (E)-2-Methyl-1-phenyl-N-(pyridin-2-ylmethylene)propan-1-amine, as a yellow oil (0.379 g, 92% yield). After heating the reaction mixture was concentrated under reduced pressure dried under high vacuum

Conditions: temp:60.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To 2-methoxy-N-(2-methyl-1-phenylpropyl)aniline (1.36 g, 5.34 mmol, 1.00 equiv) in 2:1 v/v MeCN/H2O (76 mL) was added AgNO3 (0.271 g, 1.60 mmol, 0.300 equiv) and the reaction mixture was heated to 60° C. Ammonium persulfate (8.58 g, 37.6 mmol, 7.04 equiv) was added in three portions over 15 min and the reaction mixture was heated at 60° C. for 1 h. An aqueous solution of HCl (10 mL, 2 N in H2O) was added. The reaction mixture was filtered through a celite pad, eluting with H2O. The aqueous layer was washed with Et2O (3×30 mL) and the combined organic layers were washed with HCl (2×30 mL, 0.5 N in H2O). The combined aqueous layers were basified with 2.5 M NaOH and the aqueous layer was extracted with Et2O (4×20 mL). The combined organic layers were washed with brine, dried over MgSO4, filtered, and concentrated. The residue was purified by Kugelrohr distillation (50 mTorr, 60° C.) to give 2-methyl-1-phenylpropan-1-amine as a colorless oil (0.257 g, 32% yield). the reaction mixture was heated at 60° C. for 1 h The reaction mixture was filtered through a celite pad eluting with H2O The aqueous layer was washed with Et2O (3×30 mL) the combined organic layers were washed with HCl (2×30 mL, 0.5 N in H2O) the aqueous layer was extracted with Et2O (4×20 mL) The combined organic layers were washed with brine dried over MgSO4 filtered concentrated The residue was purified by Kugelrohr distillation (50 mTorr, 60° C.)