Ethanol → (1S)-1-(8-fluoro-2-(2-(methylsulfonyl)phenyl)quinolin-3-yl)ethanamine

HRID 1019792Notes

Reaction equation

[F:1][C:2]1[CH:3]=[CH:4][CH:5]=[C:6]2[C:11]=1[N:10]=[C:9]([C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][C:13]=1[S:18]([CH3:21])(=[O:20])=[O:19])[C:8]([C@@H:22]([N:24]1C(=O)C3C(=CC=CC=3)C1=O)[CH3:23])=[CH:7]2.O.NN.CCO>CCOC(C)=O>[F:1][C:2]1[CH:3]=[CH:4][CH:5]=[C:6]2[C:11]=1[N:10]=[C:9]([C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][C:13]=1[S:18]([CH3:21])(=[O:19])=[O:20])[C:8]([C@@H:22]([NH2:24])[CH3:23])=[CH:7]2

Participants

Conditions

Temperature: 65 °C

Procedure

2-((1S)-1-(8-Fluoro-2-(2-(methylsulfonyl)phenyl)quinolin-3-yl)ethyl)isoindoline-1,3-dione (9.10 g, 19.2 mmol), and hydrazine hydrate (9.32 mL, 192 mmol) were added to EtOH (190 mL). After heating at 65° C. for 3 h, the resultant slurry was cooled to rt, diluted with 900 mL of EtOAc, and filtered through a fitted funnel. The filtrate was washed with H2O (3×200 mL), brine (1×200 mL) and then dried over MgSO4 before being concentrated under vacuum to give (1S)-1-(8-fluoro-2-(2-(methylsulfonyl)phenyl)quinolin-3-yl)ethanamine (6.06 g, 17.6 mmol, 92% yield) as a light orange solid. The proton NMR reflects a 73/27 ratio of atropisomers at 25° C. 1H NMR (500 MHz, CDCl3) δ ppm 8.55 (d, J=1.5 Hz, 0.73H), 8.50 (d, J=1.5 Hz, 0.27H), 8.26 (dd, J=8.1, 1.2 Hz, 0.27H), 8.23 (dq, J=7.8 1.2 Hz, 0.73H), 7.73 (m, 3H), 7.52 (m, 1.27H), 7.40 (m, 1.73H), 4.16 (q, J=6.6 Hz, 0.27H), 4.03 (q, J=6.4 Hz, 0.73H), 3.36 (s, 0.79H), 3.17 (s, 2.21H), 1.36 (m, 3H). Mass Spectrum (ESI) m/e=345.2 (M+1).

Workup

temperaturethe resultant slurry was cooled to rt
filtrationfiltered through a fitted funnel
washThe filtrate was washed with H2O (3×200 mL), brine (1×200 mL)
dry with materialdried over MgSO4
concentrationbefore being concentrated under vacuum

Sources & evidence

ORD record: ord-feeaabe0da704f65a1293800b3ac28b2
Source dataset: uspto-grants-2014_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08716290B2

Reaction notes

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