Water → (S)-8-Fluoro-5-(4-methoxy-benzenesulfonyl)-6-methyl-5,6-dihydrophenanthridine

HRID 2181820Notes

Reaction equation

F[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[C:8]1[CH:13]=[CH:12][C:11]([F:14])=[CH:10][C:9]=1[C@@H:15]([NH:17][S:18]([C:21]1[CH:26]=[CH:25][C:24]([O:27][CH3:28])=[CH:23][CH:22]=1)(=[O:20])=O)[CH3:16].C(=O)([O-])[O-].[K+].[K+].[OH2:35]>CN(C)C=O>[F:14][C:11]1[CH:10]=[C:9]2[C:8](=[CH:13][CH:12]=1)[C:3]1[CH:2]=[CH:7][CH:6]=[CH:5][C:4]=1[N:17]([S:18]([C:21]1[CH:22]=[CH:23][C:24]([O:27][CH3:28])=[CH:25][CH:26]=1)(=[O:20])=[O:35])[C@H:15]2[CH3:16]

Participants

Conditions

Temperature: 100 °C

Procedure

A stirred suspension of N-[(1S)-1-(2′,4-difluoro-1,1′-biphenyl-2-yl)ethyl]-4-methoxybenzenesulfonamide (1.7 g, 4.2 mmol) and potassium carbonate (1.16 g, 8.4 mmol) in N,N-dimethylformamide (25 mL) was heated at 100° C., and the reaction progress was monitored by LCMS. After 96 hours, water (300 mL) was added with stirring. A precipitate was filtered and washed with copious amounts of water. The product was purified by preparative liquid chromatography on a Biotage® 40 Mi column of pre-packed silica gel (90 g), eluting with a gradient of 30%-50% methyl tert-butylether in hexane, to afford a purified solid. Recrystallization of the solid afforded (6S)-8-fluoro-5-[(4-methoxyphenyl)sulfonyl]-6-methyl-5,6-dihydrophenanthridine* (1.4 g, 87%, >99.9% ee), m.p. 196.8-198° C.;

Workup

filtrationA precipitate was filtered
washwashed with copious amounts of water
customThe product was purified by preparative liquid chromatography on a Biotage® 40 Mi column of pre-packed silica gel (90 g)
washeluting with a gradient of 30%-50% methyl tert-butylether in hexane
customto afford a purified solid
customRecrystallization of the solid

Sources & evidence

ORD record: ord-c2597a6cd3a04360a8da685911a4e6c7
Source dataset: uspto-grants-2005_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US06894061B2

Reaction notes

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