3-Fluoro-4-methoxyphenylboronic acid → 1,2-Difluoro-4-(3-fluoro-4-methoxyphenyl)-5-[4-(methylsulfonyl)phenyl]benzene
Reaction equation
Br[C:2]1[CH:7]=[C:6]([F:8])[C:5]([F:9])=[CH:4][C:3]=1[C:10]1[CH:15]=[CH:14][C:13]([S:16]([CH3:19])(=[O:18])=[O:17])=[CH:12][CH:11]=1.[F:20][C:21]1[CH:22]=[C:23](B(O)O)[CH:24]=[CH:25][C:26]=1[O:27][CH3:28]>>[F:9][C:5]1[CH:4]=[C:3]([C:10]2[CH:15]=[CH:14][C:13]([S:16]([CH3:19])(=[O:18])=[O:17])=[CH:12][CH:11]=2)[C:2]([C:23]2[CH:24]=[CH:25][C:26]([O:27][CH3:28])=[C:21]([F:20])[CH:22]=2)=[CH:7][C:6]=1[F:8]Participants
Procedure
Following the general procedure outlined in Synthetic Scheme VI, 3.0 g (8.6 mmol) of 1-bromo-4,5-difluoro-2-[4-(methylsulfonyl)phenyl]benzene (Example 18, Step 2) was reacted with 1.9 g (11 mmol) of 3-fluoro-4-methoxyphenylboronic acid (Example 4, Step 3). Purification by silica gel chromatography (Waters Prep-500A) with ethyl acetate/hexane (1:3) and subsequent recrystallization from ethyl acetate/hexane gave 3.19 g (94%) of 1,2-difluoro-4-(3-fluoro-4-methoxyphenyl)-5-[4-(methylsulfonyl)phenyl]benzene as a colorless solid: mp 159.2-159.7° C.; NMR (CDCl3) δ 3.05 (s, 3H), 3.87 (s, 3H), 6.63-6.85 (m, 3H), 7.16-7.32 (m, 4H), 7.82 (d, J=8 Hz, 2H). MS (EI): m/e (rel intensity) 392 (49), 313 (15), 298 (48), 269 (100), 249 (79). Anal. Calc'd for C20H15F3O3S (0.26 ethyl acetate): C, 60.85; H, 4-0.15; F, 13.71. Found: C, 61.33; H, 3.90; F, 13.40.
Workup
- customPurification by silica gel chromatography (Waters Prep-500A)
- customwith ethyl acetate/hexane (1:3) and subsequent recrystallization from ethyl acetate/hexane
Sources & evidence
- ORD record
- ord-b350777a7f014479894536fd5a57fd0d
- Source dataset
- uspto-grants-2004_01
- Patent number
- US06677488B2
Reaction notes
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