5-phenylpentan-1-amine

Conditions: temp:23.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 2-(1H-Benzotriazol-1-yl)-1,1,3,3-tetramethyluronium tetrafluoroborate (1.42 g) was added to a solution of (2R,3S,4R)-3-acetylamino-4-(tert-butyldiphenylsilanyloxy)-3,4-dihydro-2H-pyran-2,6-dicarboxylic acid, 6-methyl ester (2 g) and N,N-diisopropylethylamine (1.4 ml) in dimethylformamide (5 ml), under nitrogen. To this was added N-phenethylpropylamine (722 mg) and the reaction was stirred at 23° C. for 16 hours. The solvent was removed in vacuo and the residue was partitioned between water and ethyl acetate. The organic extracts were dried over anhydrous sodium sulphate and the solvent was removed in vacuo to give a fawn foam. The foam was chromatographed over silica (Merck 9385, 45 g) using medium pressure (ca 4 psi) and ethyl acetate/cyclohexane (1:2 v/v) as the eluant. The required fractions were combined and the solvent removed in vacuo to give the title compound as a white foam (1.1 g). 1H NMR (250 MHz, CDCl3, rotamers) 7.6--7.1 (15H, m), 6.0+5.95 (1H, 2×m), 5.9--5.8 (1H, 2×d, J=6Hz), 5.2 (1H, 2×d, J=5Hz), 4.6 (1H, 2×d, J=3Hz), 4.0--3.7 (1H, m), 3.8 (3H, 2×s), 3.5--2.9 (4H, m), 2.8+2.5 (2H, 2×m), 2.0 (3H, 2×s), 1.5 --1.2 (2H, m), 1.1 (9H, s), 0.9+0.7 (3H, 2×t, J=7Hz). The solvent was removed in vacuo the residue was partitioned between water and ethyl acetate The organic extracts were dried over anhydrous sodium sulphate the solvent was removed in vacuo to give a fawn foam The foam was chromatographed over silica (Merck 9385, 45 g) the solvent removed in vacuo

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 5-phenylpentan-1-amine (0.07 g, 0.43 mmol) was dissolved in dry dichloromethane (4.5 mL). The solution was cooled to 0° C. and saturated aqueous NaHCO3 solution (4.5 mL) was added. The biphasic mixture was stirred for 10 min at 0° C., the layers were allowed to separate then a solution of triphosgene (0.51 g, 0.52 mmol) in dry toluene (2.5 mL) was added to the organic layer. After 15 min the aqueous layer was extracted with dichloromethane (3×10 mL). The combined organic layers were dried over Na2SO4 and the solvent was removed under reduced pressure. The resulting residue was added to a solution of uracil (0.05 g, 0.43 mmol) and DMAP (0.01 g, 0.01 mmol) in dry pyridine (5 mL). The suspension was stirred at room temperature for 18 hrs. The crude was purified by column chromatography using a Teledyne ISCO apparatus (cyclohexane:EtOAc 75:25) to afford the title compound (0.04 g, 32%) as a white solid. 1H NMR (400 MHz, DMSO-d6): 1.25-1.42 (m, 2H), 1.46-1.64 (m, 5H), 2.54-2.60 (m, 2H), 3.21-3.28 (m, 2H), 5.79 (d, J=8.38 Hz, 1H), 7.06-7.36 (m, 5H), 8.20 (d, J=8.40 Hz, 1H), 9.11 (t, J=5.65 Hz, 1H), 11.71 (s, 1H). 13C NMR (101 MHz, DMSO-d6) δ 26.18, 28.56, 30.79, 35.12, 41.81, 40.26, 103.48, 125.78, 128.11, 129.30, 139.70, 149.23, 151.13, 161.80. to separate After 15 min the aqueous layer was extracted with dichloromethane (3×10 mL) The combined organic layers were dried over Na2SO4 the solvent was removed under reduced pressure The suspension was stirred at room temperature for 18 hrs The crude was purified by column chromatography

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

Procedure: Hydrazine monohydrate (0.36 g, 7.2 mmol) was added to a solution of 2-(5-phenylpentyl)isoindoline-1,3-dione (0.68 g, 2.3 mmol) in 25 mL of EtOH. The solution was stirred under reflux for 5 hrs and then cooled to room temperature. The white precipitate was removed by filtration and the filtrate was concentrated under reduced pressure. The residue was dissolved in a 1N solution of NaOH (80 mL) and extracted with chloroform (3×70 mL). The combined organic layers were washed with brine, dried over Na2SO4 and the solvent was removed under reduced pressure. The crude was purified by column chromatography using a Teledyne ISCO apparatus (solid deposition with TEA, eluent: 20% MeOH in dichloromethane with 1% of TEA) to afford the title compound (0.28 g, 73%) as a white solid. 1H NMR (400 MHz, CDCl3): 1.37-1.48 (m, 2H), 1.58-1.72 (m, 4H), 2.57-2.69 (m, 2H), 3.29 (t, J=6.70 Hz, 2H), 7.13-7.24 (m, 3H), 7.26-7.34 (m, 2H). under reflux for 5 hrs The white precipitate was removed by filtration the filtrate was concentrated under reduced pressure The residue was dissolved in a 1N solution of NaOH (80 mL) extracted with chloroform (3×70 mL) The combined organic layers were washed with brine dried over Na2SO4 the solvent was removed under reduced pressure The crude was purified by column chromatography