| 70% |
With sodium tris(acetoxy)borohydride; acetic acid; In dichloromethane; at 20℃; for 15h;Product distribution / selectivity; |
A solution of (S)-(-)-1-(4-methoxyphenyl)ethylamine (25 g, 166 mmol) and 6,7- dihydro-8(5H)-quinolinone (24 g, 166 mmol) in dichloromethane was treated with glacial acetic acid (14 ml_, 249 mmol) and sodium triacetoxyborohydride (53 g, 249 mmol). The reaction mixture was stirred at room temperature for 15 hours and treated with sodium carbonate (106 g, 996 mmol) and stirred for 30 minutes. The mixture was diluted with dichloromethane, the organic layer separated, and the aqueous extracted with more dichloromethane. The organic layers were combined, dried over magnesium sulfate, concentrated, and purified by column chromatography (0-3% 2 M ammonia in methanol/dichloromethane) to give a yellow oil which was crystallized from hexanes to yield (8S)-Lambda/-{(1S)-1-[4-(methyloxy)phenyl]ethyl}-5,6,7,8- tetrahydro-8-quinolinamine (33 g, 70% yield) as clear crystals. 1H-NMR (CDCI3): delta 8.40 (m, 1 H), 7.33 (m, 3H), 7.04 (m, 1 H), 6.84 (d, 2H), 4.02 (m, 1H), 3.83-3.78 (m, 4H), 2.73-2.62 (m, 2H), 1.82 (m, 1 H), 1.72 (m, 1 H), 1.57 (m, 2H), 1.43 (d, 3H). |
| 70% |
|
A solution of (S)-(-)-1-(4-methoxyphenyl)ethylamine (25.0 g, 166 mmol) and 6,7-dihydro-8(5f/)-quinolinone (24.0 g, 166 mmol, J. Org. Chem., 2002, 67, 2197-2205) in dichloromethane was treated with glacial acetic acid (14.0 mL, 249 mmol) and sodium triacetoxyborohydride (53.0 g, 249 mmol). The reaction mixture was stirred at room temperature for 15 hours and then treated with sodium carbonate (106 g, 996 mmol) dissolved in water. The resulting mixture was stirred for 30 minutes and then diluted with dichloromethane. The phases were separated and the aqueous solution extracted with an additional portion of dichloromethane. The combined organic solutions were dried over MgSO4 and concentrated to dryness at reduced pressure. The crude product was <n="35"/>purified by flash chromatography (silica gel, gradient elution of dichloromethane to 97:3 dichloromethane/2M ammonia in MeOH) followed by recrystallization from hexane to afford 33 g (70%) of (8S)-Lambda/-{(1 S)-1-[4-(methyloxy)phenyl]ethyl}-5,6,7,8-tetrahydro-8- quinolinamine as a white crystalline solid. 1H NMR (CDCI3): delta 8.40 (m, 1 H), 7.33 (m, 3H), 7.04 (m, 1 H), 6.84 (d, 2H), 4.02 (m, 1 H), 3.83-3.78 (m, 4H), 2.73-2.62 (m, 2H), 1.82 (m, 1H), 1.72 (m, 1 H), 1.57 (m, 2H), 1.43 (d, 3H). |
| 70% |
|
A solution of (S)-(-)-1-(4-methoxyphenyl)ethylamine (25 g, 166 mmol) and 6,7- dihydro~8(5W)-quinolinone (24 g, 166 mmol) in dichloromethane was treated with glacial acetic acid (14 mL, 249 mmol) and sodium triacetoxyborohydride (53 g, 249 mmol). The reaction mixture was stirred at room temperature for 15 hours and treated with sodium carbonate (106 g, 996 mmol) and stirred for 30 minutes. The mixture was diluted with dichloromethane, the organic layer separated, and the aqueous extracted with more dichloromethane. The organic layers were combined, dried over magnesium sulfate, concentrated, and purified by column chromatography (0-3% 2 M ammonia in methanol/dichloromethane) to give a yellow oil which was crystallized from hexanes to yield (8S)-Lambda/-{(1S)-1-[4-(methyloxy)phenyl]ethyl}-5,6,7,8- tetrahydro-8-quinolinamine (33 g, 70% yield) as clear crystals. 1H-NMR (CDCI3): delta 8.40 (m, 1H), 7.33 (m, 3H), 7.04 (m, 1H), 6.84 (d, 2H), 4.02 (m, 1H), 3.83-3.78 (m, 4H), 2.73-2.62 (m, 2H), 1.82 (m, 1H), 1.72 (m, 1H), 1.57 (m, 2H), 1.43 (d, 3H). |
| 63% |
With sodium tris(acetoxy)borohydride; In dichloromethane; at 22℃; for 24h;Product distribution / selectivity; |
A slurry of sodium triacetoxyborohydride (4.54 Kg, 21.4 mol.) in dichloromethane (22 Liters) is treated with 6,7-dihydro-8(5/-/)-quinolinone (1.8 Kg, 12.3 mol.) followed by (1 S)-1-[4-(methyloxy)phenyl]ethanamine (1.8 Kg, 11.9 mol).) and the reaction was allowed to stirr vigorously at 22 0C for 24 hrs. The reaction is quenched with 1 N NaOH (aprox 27 Liters) to achieve pH 8 in the aqueous layer. The phases were separated and the organic phase was treated with 1 N sodium hydroxide ( aprox 3.5 Liters) to achieve pH 11 in the aqueous layer. The phases again separated. The dichloromethane solution was then concentrated to minimum volume and treated with heptane (18 Liters). The volume again concentrated to aprox 9 Liters. Precipitation occurred upon cooling to 22 0C. The suspension was further cooled to 0 0C. and filtered. Solids were dried at ambient temperature under vacuum with nitrogen to give (8S)-Lambda/-{(1 S)-1-[4-(methyloxy)phenyl]ethyl}-5,6,7,8-tetrahydro-8- quinolinamine. (2.18 Kg, 63%) 1 H NMR (400 MHz, DMSO-D6) delta ppm 8.36 (m, 1 H) 7.44 (m, 1 H) 7.29 (m, 2 H) 7.15 (m, 1 H) 6.83 (m, 2 H) 4.00 (m, 1 H) 3.70 (s, 3 H) 3.59 - 3.64 (m, 1 H) 2.66 (m, 1 H) 2.64 (s, 1 H) 2.53 (s, 1 H) 1.76 (s, 1 H) 1.64 (s, 1 H) 1.50 (s, 1 H) 1.39 (s, 1 H) 1.24 (m, 3 H) |
| 63% |
With sodium tris(acetoxy)borohydride; In dichloromethane; at 22℃; for 24h;Product distribution / selectivity; |
A slurry of sodium triacetoxyborohydride (4.54 Kg, 21.4 mol.) in dichloromethane (22 Liters) is treated with 6,7-dihydro-8(5/-/)-quinolinone (1.8 Kg, 12.3 mol.) followed by (1S)-1-[4-(methyloxy)phenyl]ethanamine (1.8 Kg, 11.9 mol).) and the reaction was allowed to stirr vigorously at 22 0C for 24 hrs. The reaction is quenched with 1 N NaOH (aprox 27 Liters) to achieve pH 8 in the aqueous layer. The phases were separated and the organic phase was treated with 1N sodium hydroxide ( aprox 3.5 Liters) to achieve pH 11 in the aqueous layer. The phases again separated. The dichloromethane solution was then concentrated to minimum volume and treated with heptane (18 Liters). The volume again concentrated to aprox 9 Liters. Precipitation occurred upon cooling to 22 0C. The suspension was further cooled to 00C. and filtered. Solids were dried at ambient temperature under vacuum with nitrogen to give (8S)-N-{(1S)-1-[4-(methyloxy)phenyl]ethyl}-5,6,7,8-tetrahydro-8- quinolinamine. (2.18 Kg, 63%) 1H NMR (400 MHz, DMSO-D6) delta ppm 8.36 (m, 1 H) 7.44 (m, 1 H) 7.29 (m, 2 H) 7.15 (m, 1 H) 6.83 (m, 2 H) 4.00 (m, 1 H) 3.70 (s, 3 H) 3.59 - 3.64 (m, 1 H) 2.66 (m, 1 H) 2.64 (s, 1 H) 2.53 (s, 1 H) 1.76 (s, 1 H) 1.64 (s, 1 H) 1.50 (s, 1 H) 1.39 (s, 1 H) 1.24 (m, 3 H) |
| 58% |
With sodium tris(acetoxy)borohydride; In dichloromethane; at 20℃; |
A slurry of sodium triacetoxyborohydride (3.55?g, 16.7?mmol) in dichloromethane (60?mL) was treated with 36 [ 31 ] (1.37?g, 9.3?mmol), followed by (S)-1-(4-methoxyphenyl)ethanamine (1.41?g, 9.3?mmol). The reaction was stirred vigorously at room temperature overnight. The reaction was quenched with 1?N NaOH (20?mL) to adjust pH?=?8. The organic layer was separated, dried over Na2SO4, and concentrated. The resulting residue was purified by silica gel column chromatography (dichloromethane/methanol?=?50/1) to give the desired product (1.5?g, 58%) as a yellow oil. [alpha]D25 = +34 (c?=?0.2, MeOH). 1H NMR (400?MHz, DMSO-d6) delta 8.38 (d, J?=?4.0?Hz, 1H), 7.47 (d, J?=?7.2?Hz, 1H), 7.31 (d, J?=?8.4?Hz, 2H), 7.20-7.15 (m, 1H), 6.85 (d, J?=?8.8?Hz, 2H), 4.04-3.99 (m, 1H), 3.72 (s, 3H), 3.65-3.62 (m, 1H), 2.75-2.69 (m, 2H), 1.83-1.73 (m, 1H), 1.69-1.59 (m, 1H), 1.57-1.48 (m, 1H), 1.45-1.38 (m, 1H), 1.26 (d, J?=?7.2?Hz, 3H). |
Chemistry
Pharmaceutical Intermediates
Inhibitors/Agonists
Material Science
HazMat Fee +
For Research Only
110K+ Compounds
Competitive Price
1-2 Day Shipping
