4-trimethylsilylbenzaldehyde

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

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

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

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

Procedure: Bromo-4-(trimethylsilyl)benzene (1.15 g, 5 mmol) was dissolved in THF (30 ml) and cooled to −78° C. Under argon a 1.6 M solution of n-butyl lithium in hexane (3.13 ml, 5 mmol) was added dropwise keeping the temperature below −70° C. The clear colorless solution was stirred at −78° C. for 15 min and DMF (1.156 ml, 15 mmol) was added quickly. The reaction temperature increased to −68° C. The reaction was stirred for additional 15 min at −78° C., quenched with 1N aqueous hydrogen chloride solution and extracted twice with diethyl ether. The combined organic layers were washed twice with water and once with saturated aqueous sodium chloride solution, dried over sodium sulfate, filtered and the solvent was evaporated to leave the product as a colorless oil (920 mg, 100%). The product was pure enough to be used directly in the next step. MS (ISP) 179.2 (M+H+). 1H NMR (CDCl3, 300 MHz): δ 10.02 (s, 1H) 7.84 (d, 2H), 7.69 (d, 2H), 0.31 (s, 9H). the temperature below −70° C The reaction temperature increased to −68° C The reaction was stirred for additional 15 min at −78° C. quenched with 1N aqueous hydrogen chloride solution extracted twice with diethyl ether The combined organic layers were washed twice with water and once with saturated aqueous sodium chloride solution dried over sodium sulfate filtered the solvent was evaporated

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

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

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

Procedure: Bromo-4-(trimethylsilyl)benzene (1.15 g, 5 mmol) was dissolved in THF (30 ml) and cooled to −78° C. Under argon a 1.6 M solution of n-butyl lithium in hexane (3.13 ml, 5 mmol) was added dropwise keeping the temperature below −70° C. The clear colorless solution was stirred at −78° C. for 15 min and DMF (1.156 ml, 15 mmol) was added quickly. The reaction temperature increased to −68° C. The reaction was stirred for additional 15 min at −78° C., quenched with 1N aqueous hydrogen chloride solution and extracted twice with diethyl ether. The combined organic layers were washed twice with water and once with saturated aqueous sodium chloride solution, dried over sodium sulfate, filtered and the solvent was evaporated to leave the product as a colorless oil (920 mg, 100%). The product was pure enough to be used directly in the next step. MS (ISP) 179.2 (M+H+). 1H NMR (CDCl3, 300 MHz): δ 10.02 (s, 1H) 7.84 (d, 2H), 7.69 (d, 2H), 0.31 (s, 9H). the temperature below −70° C The reaction temperature increased to −68° C The reaction was stirred for additional 15 min at −78° C. quenched with 1N aqueous hydrogen chloride solution extracted twice with diethyl ether The combined organic layers were washed twice with water and once with saturated aqueous sodium chloride solution dried over sodium sulfate filtered the solvent was evaporated

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

Procedure: Bromo-4-(trimethylsilyl)benzene (1.15 g, 5 mmol) was dissolved in THF (30 ml) and cooled to −78° C. Under argon a 1.6 M solution of n-butyl lithium in hexane (3.13 ml, 5 mmol) was added dropwise keeping the temperature below −70° C. The clear colorless solution was stirred at −78° C. for 15 min and DMF (1.156 ml, 15 mmol) was added quickly. The reaction temperature increased to −68° C. The reaction was stirred for additional 15 min at −78° C., quenched with 1N aqueous hydrogen chloride solution and extracted twice with diethyl ether. The combined organic layers were washed twice with water and once with saturated aqueous sodium chloride solution, dried over sodium sulfate, filtered and the solvent was evaporated to afford the product as a colorless oil (920 mg, 100%). The product was pure enough to be used directly in the next step. MS (ISP) 179.2 (M+H+). 1HNMR (CDCl3, 300 MHz): δ 10.02 (s, 1H) 7.84 (d, 2H), 7.69 (d, 2H), 0.31 (s, 9H). the temperature below −70° C The reaction temperature increased to −68° C The reaction was stirred for additional 15 min at −78° C. quenched with 1N aqueous hydrogen chloride solution extracted twice with diethyl ether The combined organic layers were washed twice with water and once with saturated aqueous sodium chloride solution dried over sodium sulfate filtered the solvent was evaporated

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

Procedure: [2-(4-fluoro-phenyl)-ethyl]-(4-trimethylsilanyl-benzyl)-amine was prepared in analogy to example 1 from 4-trimethylsilanyl-benzaldehyde and 2-(4-fluoro-phenyl)-ethylamine. MS (ISP): 302.2 (100) (M+H)+. 1H NMR (CDCl3, 300 MHz): δ 7.47 (d, 2H), 7.27 (d, 2H), 7.15 (dd, 2H), 6.97 (dt, 2H) 3.79 (s, 2H), 2.75-3.00 (m, 4H), 0.26 (s, 9H).

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

Procedure: [2-(4-chloro-phenyl)-ethyl]-(4-trimethylsilanyl-benzyl)-amine was prepared in analogy to example 1 from 4-trimethylsilanyl-benzaldehyde and 2-(4-chloro-phenyl)-ethylamine. MS (ISP): 318.1/320.3 (100/39) (M+H)+. 1HNMR (CDCl3, 300 MHz): δ 7.47 (d, 2H), 7.23-7.28 (m, 4H), 7.12 (d, 2H), 3.79 (s, 2H), 2.75-3.00 (m, 4H), 0.26 (s, 9H).

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

Procedure: [2-(3-trifluoromethyl-phenyl)-ethyl]-(4-trimethylsilanyl-benzyl)-amine was prepared in analogy to example 1 from 4-trimethylsilanyl-benzaldehyde and 2-(3-trifluoromethyl-phenyl)-ethylamine. MS (ISP): 352.3 (M+H)+. 1HNMR (CDCl3, 300 MHz): δ 7.48 (m, 4H), 7.39 (m, 2H), 7.27 (d, 2H), 3.81 (s, 2H), 2.80-3.00 (m, 4H), 0.26 (s, 9H).

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

Procedure: 4-Trimethylsilanyl-benzaldehyde (800 mg, 4.5 mmol) and 2-(3,4-dichloro-phenyl)-ethylamine (1023 mg, 5.4 mmol) were dissolved in methanol (5 ml) and the solution was stirred at rt for 5 min. Sodium borohydride (166 mg, 4.5 mmol) was added under nitrogen and the reaction mixture was stirred at rt for 1 h. Water was added and methanol was evaporated in vacuo. The reaction was extracted twice with diethyl ether and the combined organic layers were washed once with water and once with sat. aq. NaCl solution, dried with sodium sulfate, filtered and concentrated in vacuo to yield [2-(3,4-dichloro-phenyl)-ethyl]-(4-trimethylsilanyl-benzyl)-amine (1640 mg, 100%) as a colorless oil. MS (ISP): 352.2/354.2 (100/74) (M+H)+. 1HNMR (CDCl3, 300 MHz): δ 7.48 (d, 2H), 7.25-7.35 (m, 4H), 7.02 (dd, 2H), 3.79 (s, 2H), 2.75-3.00 (m, 4H), 0.26 (s, 9H). the reaction mixture was stirred at rt for 1 h methanol was evaporated in vacuo The reaction was extracted twice with diethyl ether the combined organic layers were washed once with water and once with sat. aq. NaCl solution dried with sodium sulfate filtered concentrated in vacuo