3-(4-bromophenyl)propan-1-amine

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

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

Procedure: To a solution of Boc-glycine 130 (1.04 g, 5.88 mmol) and 4-bromobenzylethylamine 131 (1.00 g, 4.90 mmol) in CH2Cl2 (25 mL) at room temperature was added Hunig's base (1.30 mL, 7.35 mmol). The mixture was stirred at room temperature for 16 h. The mixture was poured into water (40 mL) and sat. NaHCO3 (3 mL), then extracted with CH2Cl2 (60 mL), washed with water (100 mL), and dried with Na2SO4. The residue was isolated by column chromatography (50/50/0.1 EtOAc/Hexane/NH4OH), to give 1.30 g of amide 132 as a white crystalline solid in 69% yield. 1HNMR (300 MHz, CDCl3, ppm): δ: 7.37 (d, J=7 Hz, 2H), 7.09 (d, J=7 Hz, 1H), 6.50 (s br, 1H), 5.15 (s br, 1H), 5.01-4.95 (m, 1H), 3.69 (d, J=6 Hz, 2H), 1.39 (d, J=7 Hz, 3H), 1.37 (s, 9H). extracted with CH2Cl2 (60 mL) washed with water (100 mL) dried with Na2SO4

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

Procedure: 3-(4-Bromophenyl)propan-1-amine (0.50 g, 2.34 mmol; described in: Davies, R. V. et al. J. Chem. Soc. Perkin Trans. 1 1977, 2357-2364), cyclobutanone (0.393 g, 5.61 mmol) and acetic acid (0.140 mL, 2.34 mmol) were mixed in dichloroethane (6 mL) and stirred for 30 min. Sodium triacetoxy borohydride was added and the reaction mixture was stirred for 15 h. The reaction was quenched with water (15 mL) and extracted with methylene chloride (50 mL). The organic phase was separated, dried and evaporated. Purification by column chromatography using methylene chloride to methylene chloride/methanol, (2:1), gradient as the eluent gave 0.32 g (42% yield) of the title compound as colorless oil: MS (ESI) m/z 322 and 324 (M++1). the reaction mixture was stirred for 15 h The reaction was quenched with water (15 mL) extracted with methylene chloride (50 mL) The organic phase was separated dried evaporated Purification by column chromatography

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

Procedure: To a solution of Boc-glycine 130 (1.04 g, 5.88 mmol) and 4-bromobenzylethylamine 131 (1.00 g, 4.90 mmol) in CH2Cl2 (25 mL) at room temperature was added Hunig's base (1.30 mL, 7.35 mmol). The mixture was stirred at room temperature for 16 h. The mixture was poured into water (40 mL) and sat. NaHCO3 (3 mL), then extracted with CH2Cl2 (60 mL), washed with water (100 mL), and dried with Na2SO4. The residue was isolated by column chromatography (50/50/0.1 EtOAc/Hexane/NH4OH), to give 1.30 g of amide 132 as a white crystalline solid in 69% yield. 1HNMR (300 MHz, CDCl3, ppm): δ: 7.37 (d, J=7 Hz, 2H), 7.09 (d, J=7 Hz, 1H), 6.50 (s br, 1H), 5.15 (s br, 1H), 5.01-4.95 (m, 1H), 3.69 (d, J=6 Hz, 2H), 1.39 (d, J=7 Hz, 3H), 1.37 (s, 9H). extracted with CH2Cl2 (60 mL) washed with water (100 mL) dried with Na2SO4

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

Procedure: To a solution of Boc-glycine 130 (1.04 g, 5.88 mmol) and 4-bromobenzylethylamine 131 (1.00 g, 4.90 mmol) in CH2Cl2 (25 mL) at room temperature was added Hunig's base (1.30 mL, 7.35 mmol). The mixture was stirred at room temperature for 16 h. The mixture was poured into water (40 mL) and sat. NaHCO3 (3 mL), then extracted with CH2Cl2 (60 mL), washed with water (100 mL), and dried with Na2SO4. The residue was isolated by column chromatography (50/50/0.1 EtOAc/Hexane/NH4OH), to give 1.30 g of amide 132 as a white crystalline solid in 69% yield. 1HNMR (300 MHz, CDCl3, ppm): δ: 7.37 (d, J=7 Hz, 2H), 7.09 (d, J=7 Hz, 1H), 6.50 (s br, 1H), 5.15 (s br, 1H), 5.01-4.95 (m, 1H), 3.69 (d, J=6 Hz, 2H), 1.39 (d, J=7 Hz, 3H), 1.37 (s, 9H). extracted with CH2Cl2 (60 mL) washed with water (100 mL) dried with Na2SO4

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

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

Procedure: A mixture of 3-(4-bromophenyl)-propylamine (6.21 g, 29 mmol), 2-bromomethyl-benzoic acid methyl ester (6.57 g, 29 mmol), and K2CO3 (6.91 g, 50 mmol) in toluene (100 mL) was heated at reflux with stirring for 1.5 h. Workup and silica gel column chromatography using a gradient of hexanes to 50% ethyl acetate in hexanes afforded 2-[3-(4-bromophenyl)-propyl]-2,3-dihydroisoindol-1-one (7.24 g, 88%). GC/MS gave: m/z (rel.int.) 331 (M+, 9), 329 (M+, 9), 147 (100), 146 (54) 119 (34), and 91 (33). 1H NMR (300 MHz, CDCl3): δ 1.97 (dt, 2H), 2.64 (t, 2H), 3.66 (t, 2H), 4.35 (s, 2H), 7.08 (dd, 2H), 7.38 (dd, 2H), 7.46 (m, 2H), 7.51 (dt, 1H), 7.85 (d, 1H). 13C NMR (300 MHz, CDCl3): δ 29.9, 32.5, 41.9, 49.9, 119.7, 122.7, 123.6, 128.0, 130.2 (2C), 131.2, 131.4 (2C) 132.9, 140.3, 141.1, 168.5. was heated at reflux

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

Procedure: To a solution of 3-(4-bromophenyl)propanamide (1.59 g) in tetrahydrofuran (24 ml) was added lithium aluminum hydride (370 mg) and the mixture was refluxed for 1.5 hours under nitrogen atmosphere. After cooling to room temperature, the reaction mixture was poured into 1N aqueous sodium hydroxide solution (100 ml). The mixture was extracted with ethyl acetate and the organic layer was washed with water and brine and dried over magnesium sulfate. Filtration followed by evaporation under reduced pressure gave 3-(4-bromophenyl)-1-propanamine (1.55 g) as a yellow oil. the mixture was refluxed for 1.5 hours under nitrogen atmosphere The mixture was extracted with ethyl acetate the organic layer was washed with water and brine dried over magnesium sulfate Filtration followed by evaporation under reduced pressure

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

Procedure: To a solution of Boc-glycine 130 (1.04 g, 5.88 mmol) and 4-bromobenzylethylamine 131 (1.00 g, 4.90 mmol) in CH2Cl2 (25 mL) at room temperature was added Hunig's base (1.30 mL, 7.35 mmol). The mixture was stirred at room temperature for 16 h. The mixture was poured into water (40 mL) and sat. NaHCO3 (3 mL), then extracted with CH2Cl2 (60 mL), washed with water (100 mL), and dried with Na2SO4. The residue was isolated by column chromatography (50/50/0.1 EtOAc/Hexane/NH4OH), to give 1.30 g of amide 132 as a white crystalline solid in 69% yield. 1H NMR (300 MHz, CDCl3, ppm): δ: 7.37 (d, J=7 Hz, 2H), 7.09 (d, J=7 Hz, 1H), 6.50 (s br, 1H), 5.15 (s br, 1H), 5.01-4.95 (m, 1H), 3.69 (d, J=6 Hz, 2H), 1.39 (d, J=7 Hz, 3H), 1.37 (s, 9H). extracted with CH2Cl2 (60 mL) washed with water (100 mL) dried with Na2SO4

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

Procedure: 3-(4-Bromophenyl)propan-1-amine (0.50 g, 2.34 mmol; described in: Davies, R. V. et al. J. Chem. Soc. Perkin Trans. 1 1977, 2357-2364), cyclobutanone (0.393 g, 5.61 mmol) and acetic acid (0.140 mL, 2.34 mmol) were mixed in dichloroethane (6 mL) and stirred for 30 min. Sodium triacetoxy borohydride was added and the reaction mixture was stirred for 15 h. The reaction was quenched with water (15 mL) and extracted with methylene chloride (50 mL). The organic phase was separated, dried and evaporated. Purification by column chromatography using methylene chloride to methylene chloride/methanol, (2:1), gradient as the eluent gave 0.32 g (42% yield) of the title compound as colorless oil: MS (ESI) m/z 322 and 324 (M++1). the reaction mixture was stirred for 15 h The reaction was quenched with water (15 mL) extracted with methylene chloride (50 mL) The organic phase was separated dried evaporated Purification by column chromatography

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

Procedure: To a solution of Boc-glycine 130 (1.04 g, 5.88 mmol) and 4-bromobenzylethylamine 131 (1.00 g, 4.90 mmol) in CH2Cl2 (25 mL) at room temperature was added Hunig's base (1.30 mL, 7.35 mmol). The mixture was stirred at room temperature for 16 h. The mixture was poured into water (40 mL) and sat. NaHCO3 (3 mL), then extracted with CH2Cl2 (60 mL), washed with water (100 mL), and dried with Na2SO4. The residue was isolated by column chromatography (50/50/0.1 EtOAc/Hexane/NH4OH), to give 1.30 g of amide 132 as a white crystalline solid in 69% yield. 1HNMR (300 MHz, CDCl3, ppm): δ: 7.37 (d, J=7 Hz, 2H), 7.09 (d, J=7 Hz, 1H), 6.50 (s br, 1H), 5.15 (s br, 1H), 5.01-4.95 (m, 1H), 3.69 (d, J=6 Hz, 2H), 1.39 (d, J=7 Hz, 3H), 1.37 (s, 9H). extracted with CH2Cl2 (60 mL) washed with water (100 mL) dried with Na2SO4