3-(4-propan-2-ylphenyl)propanal

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 amine 15 (670 mg, 2.40 mmol) in 1:1 CH2Cl2:MeOH (30 mL) was added solid NaHCO3 (200 mg, 2.40 mmol) and, after 10 minutes, 3-(4-isopropylphenyl)propionaldehyde (420 mg, 2.40 mmol). After stirring for 5 minutes, NaBH(OAc)3 (760 mg, 3.60 mmol) was added, and the mixture was stirred at room temperature for 12 hours. The reaction mixture was brought to pH 8 with solid NaOH and concentrated under reduced pressure. Purification by flash chromatography (silica, 95:5 CH2Cl2:MeOH followed by 89:10:1 CH2Cl2:MeOH:NH4OH), followed by formation of the HCl salt and recrystallization (MeOH:Et2O) gave 6-(trans-4-{[3-(4-isopropylphenyl)-propyl]methylamino}cyclohexyl)-3H-benzoxazol-2-one (514 mg, 48%), as a white solid: mp 179-181° C.; IR (KBr): 2959, 1771, 1498, 1451 cm−1; 1H NMR (500 MHz, DMSO-d6): δ 11.48 (s, 1H), 10.10 (s, 1H), 7.17-7.15 (m, 5H), 7.00 (br s, 2H), 3.32-3.29 (m, 1H), 3.19-3.11 (m, 1H), 3.06-2.99 (m, 1H), 2.89-2.83 (m, 1H), 2.70 (d, J=4 Hz, 3H), 2.63-2.52 (m, 3H), 2.15-1.95 (m, 4H), 1.93-1.87 (m, 2H), 1.66-1.50 (m, 4H), 1.19 (d, J=7 Hz, 6H); ESI (m/z): 407 [M+H]+; method B, 12.69 minutes (>99%); Anal. Calcd for C26H34N2O2.HCl: C, 70.49; H, 7.96; N, 6.32. Found: C, 70.29; H, 8.05; N, 6.28. the mixture was stirred at room temperature for 12 hours concentrated under reduced pressure Purification by flash chromatography (silica, 95:5 CH2Cl2:MeOH followed by 89:10:1 CH2Cl2:MeOH:NH4OH) followed by formation of the HCl salt and recrystallization (MeOH:Et2O)

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 amine 15 (670 mg, 2.40 mmol) in 1:1 CH2Cl2:MeOH (30 mL) was added solid NaHCO3 (200 mg, 2.40 mmol) and, after 10 minutes, 3-(4-isopropylphenyl)propionaldehyde (420 mg, 2.40 mmol). After stirring for 5 minutes, NaBH(OAc)3 (760 mg, 3.60 mmol) was added, and the mixture was stirred at room temperature for 12 hours. The reaction mixture was brought to pH 8 with solid NaOH and concentrated under reduced pressure. Purification by flash chromatography (silica, 95:5 CH2Cl2:MeOH followed by 89:10:1 CH2Cl2:MeOH:NH4OH), followed by formation of the HCl salt and recrystallization (MeOH:Et2O) gave 6-(trans-4-{[3-(4-isopropylphenyl)-propyl]methylamino}cyclohexyl)-3H-benzoxazol-2-one (514 mg, 48%), as a white solid: mp 179-181° C.; IR (KBr): 2959, 1771, 1498, 1451 cm−1; 1H NMR (500 MHz, DMSO-d6): δ 11.48 (s, 1H), 10.10 (s, 1H), 7.17-7.15 (m, 5H), 7.00 (br s, 2H), 3.32-3.29 (m, 1H), 3.19-3.11 (m, 1H), 3.06-2.99 (m, 1H), 2.89-2.83 (m, 1H), 2.70 (d, J=4 Hz, 3H), 2.63-2.52 (m, 3H), 2.15-1.95 (m, 4H), 1.93-1.87 (m, 2H), 1.66-1.50 (m, 4H), 1.19 (d, J=7 Hz, 6H); ESI (m/z): 407 [M+H]+; method B, 12.69 minutes (>99%); Anal. Calcd for C26H34N2O2.HCl: C, 70.49; H, 7.96; N, 6.32. Found: C, 70.29; H, 8.05; N, 6.28. the mixture was stirred at room temperature for 12 hours concentrated under reduced pressure Purification by flash chromatography (silica, 95:5 CH2Cl2:MeOH followed by 89:10:1 CH2Cl2:MeOH:NH4OH) followed by formation of the HCl salt and recrystallization (MeOH:Et2O)