Hydrochloric Acid → Dichloromethane methanol ammonium hydroxide

To a suspension of 2-(((S)-1-(8-chloro-2-(2-fluorophenyl)quinolin-3-yl)ethyl)-carbamoyl)benzoic acid (0.6046 g, 1.347 mmol) in ethanol (5.000 mL, 1.347 mmol) was added 12 N HCl (1.123 mL, 13.47 mmol), and the mixture was stirred under reflux. After 22 h, the mixture was poured into ice water (100 mL). The mixture was basified with 10 N NaOH (0.4 mL) to pH ˜10 and extracted with CH2Cl2 (50 mL×2). The combined organic layers were washed with water (50 mL×2) and brine (50 mL×3), dried over Na2SO4, filtered, and concentrated under reduced pressure to give a mixture of 2-((S)-1-(8-chloro-2-(2-fluoro-phenyl)quinolin-3-yl)ethyl)isoindoline-1,3-dione and (1S)-1-(8-chloro-2-(2-fluorophenyl)quinolin-3-yl)ethanamine as a yellow syrup. To a mixture of 2-((S)-1-(8-chloro-2-(2-fluorophenyl)quinolin-3-yl)ethyl)isoindoline-1,3-dione and (1S)-1-(8-chloro-2-(2-fluorophenyl)quinolin-3-yl)ethanamine in ethanol (12.50 mL, 1.347 mmol) was added hydrazine monohydrate (0.4183 mL, 13.47 mmol), and the mixture was stirred under reflux. After 1 h, the mixture was cooled to room temperature and concentrated under reduced pressure to give a green solid. The green solid was purified by column chromatography on a 80 g of Redi-Sep™ column using 0% to 50% gradient of CH2Cl2:MeOH:NH4OH (89:9:1) in CH2Cl2 over 25 min and then 50% isocratic of CH2Cl2:MeOH:NH4OH (89:9:1) in CH2Cl2 for 25 min as eluent to give (1S)-1-(8-chloro-2-(2-fluorophenyl)quinolin-3-yl)-ethanamine as a light yellow syrup: 1H NMR (400 MHz, DMSO-d6) δ ppm 8.74 (1H, s), 8.03 (1H, dd, J=8.3, 1.3 Hz), 7.93 (1H, dd, J=7.5, 1.3 Hz), 7.50-7.65 (3H, m), 7.33-7.43 (2H, m), 4.03 (1H, q, J=6.3 Hz), 1.98 (2H, s), 1.16 (3H, d, J=5.5 Hz); LC-MS (ESI) m/z 301.0 [M+H]+.

1. temperatureunder reflux
2. extractionextracted with CH2Cl2 (50 mL×2)
3. washThe combined organic layers were washed with water (50 mL×2) and brine (50 mL×3)
4. dry with materialdried over Na2SO4
5. filtrationfiltered
6. concentrationconcentrated under reduced pressure
7. customto give
8. stirringthe mixture was stirred
9. temperatureunder reflux
10. waitAfter 1 h
11. concentrationconcentrated under reduced pressure
12. customto give a green solid
13. customThe green solid was purified by column chromatography on a 80 g of Redi-Sep™ column
14. customover 25 min

ORD record

ord-1067867adf9b4829902c89718f32e185

Source dataset

uspto-grants-2012_06

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08193199B2