4-Fluoro-2-(trifluoromethyl)benzeneboronic acid → 4-[4-(3,4-Dichloro-phenyl)-thiazol-2-yl]-4'-fluoro-2'-trifluoromethyl-biphenyl-2-carboxylic acid
Reaction equation
C[O:2][C:3](=[O:24])[C:4]1[CH:9]=[C:8]([C:10]2[S:11][CH:12]=[C:13]([C:15]3[CH:20]=[CH:19][C:18]([Cl:21])=[C:17]([Cl:22])[CH:16]=3)[N:14]=2)[CH:7]=[CH:6][C:5]=1Br.[F:25][C:26]1[CH:31]=[CH:30][C:29](B(O)O)=[C:28]([C:35]([F:38])([F:37])[F:36])[CH:27]=1>>[Cl:22][C:17]1[CH:16]=[C:15]([C:13]2[N:14]=[C:10]([C:8]3[CH:9]=[C:4]([C:3]([OH:2])=[O:24])[C:5]([C:29]4[CH:30]=[CH:31][C:26]([F:25])=[CH:27][C:28]=4[C:35]([F:36])([F:38])[F:37])=[CH:6][CH:7]=3)[S:11][CH:12]=2)[CH:20]=[CH:19][C:18]=1[Cl:21]Participants
Procedure
Using the conditions of General Procedure A for Suzuki Coupling and Hydrolysis in Parallel Mode, 2-bromo-5-[4-(3,4-dichloro-phenyl)-thiazol-2-yl]-benzoic acid methyl ester (which may be prepared as described for Intermediate 6; 111 mg, 0.25 mmol) was reacted with 4-fluoro-2-(trifluoromethyl)benzeneboronic acid (available from Frontier Scientific, Inc.; 87 mg, 0.5 mmol). The resulting ester was hydrolyzed and the acid was purified to give 4-[4-(3,4-dichloro-phenyl)-thiazol-2-yl]-4′-fluoro-2′-trifluoromethyl-biphenyl-2-carboxylic acid (4 mg, 3%). 1H NMR (300 MHz, DMSO-d6) δ 13.14 (br s, 1H), 8.58 (s, 1H), 8.49 (s, 1H), 8.34 (d, J=1.9 Hz, 1H), 8.26 (d, J=6.6 Hz, 1H), 8.10 (d, J=8.3 Hz, 1H), 7.77 (d, J=8.5 Hz, 1H), 7.71 (d, J=9.4 Hz, 1H), 7.57 (d, J=8.1 Hz, 2H), 7.44 (d, J=8.3 Hz, 1H).
Workup
- customthe acid was purified
Sources & evidence
- ORD record
- ord-3ab74862090849ed95ca1155a985d7f9
- Source dataset
- uspto-grants-2015_07
- Patent number
- US09073881B2
Reaction notes
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