4-Methoxybenzenesulfonyl chloride → (S)-8-Fluoro-5-(4-methoxy-benzenesulfonyl)-6-methyl-5,6-dihydrophenanthridine
Reaction equation
[F:1][C:2]1[CH:3]=[C:4]2[C:13](=[CH:14][CH:15]=1)[C:12]1[CH:11]=[CH:10][CH:9]=[CH:8][C:7]=1[NH:6][C@H:5]2[CH3:16].[CH3:17][O:18][C:19]1[CH:24]=[CH:23][C:22]([S:25](Cl)(=[O:27])=[O:26])=[CH:21][CH:20]=1>>[F:1][C:2]1[CH:3]=[C:4]2[C:13](=[CH:14][CH:15]=1)[C:12]1[CH:11]=[CH:10][CH:9]=[CH:8][C:7]=1[N:6]([S:25]([C:22]1[CH:21]=[CH:20][C:19]([O:18][CH3:17])=[CH:24][CH:23]=1)(=[O:27])=[O:26])[C@H:5]2[CH3:16]Participants
Procedure
The title compound was prepared according to the procedure of Example 19, starting from the (S)-8-Fluoro-6-methyl-5,6-dihydrophenanthridine of Example 20 (38.4 g) and 4-methoxyphenylsulfonyl chloride (37.2 g). The crude product (65.6 g) was purified by filtration over a flash silica gel plug (1 Kg) eluting with 20-25% hexane-ethyl acetate to provide 54.1 (78.4% yield) of product. The material (54.1 g) was recrystallized twice from hot 30% toluene in ethanol. The solution was seeded hot and allowed to cool to room temperature. After about 3 hours the crystalline solid was collected, rinsed with 30% toluene in ethanol (1×15 mL) and with hexane (2×15 mL), and dried to provide 27.1 g (39.3% yield based on (S)-8-fluoro-6-methyl-5,6-dihydrophenanthridine) of title compound. The compound was analyzed by chiral stationary phase HPLC (Chiralpak AD-25×0.46 cm column) on a HP1100 using 90:10 hexane-isopropanol as the mobile phase with a 1 mL/min flow rate. The analysis showed the material to be a 98.7:1.3 mixture of enantiomers,
Workup
- filtrationThe crude product (65.6 g) was purified by filtration over a flash silica gel plug (1 Kg)
- washeluting with 20-25% hexane-ethyl acetate
Sources & evidence
- ORD record
- ord-224dbc49eacd47a09d62cf26416c9029
- Source dataset
- uspto-grants-2008_05
- Patent number
- US07378427B2
Reaction notes
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