2-Chloro-6-fluorophenylboronic acid → 2'-Chloro-4-[4-(3,4-dichloro-phenyl)-thiazol-2-yl]-6'-fluoro-biphenyl-2-carboxylic acid

HRID 1519385Notes

Reaction equation

HRID 1519385 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.[Cl:25][C:26]1[CH:31]=[CH:30][CH:29]=[C:28]([F:32])[C:27]=1B(O)O>>[Cl:25][C:26]1[CH:31]=[CH:30][CH:29]=[C:28]([F:32])[C:27]=1[C:5]1[C:4]([C:3]([OH:2])=[O:24])=[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]=1

Participants

3

Reactant 2

HCID 35493952-Chloro-6-fluorophenylboronic acidHCID 86679833Methyl 2-bromo-5-(4-(3,4-dichlorophenyl)thiazol-2-yl)benzoate2×

Product 1

HCID 866798752'-Chloro-4-[4-(3,4-dichloro-phenyl)-thiazol-2-yl]-6'-fluoro-biphenyl-2-carboxylic acidYield 3%

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 2-chloro-6-fluorophenylboronic acid (available from Combi-Blocks Inc.; 87 mg, 0.5 mmol). The resulting ester was hydrolyzed and the acid was purified to give 2′-chloro-4-[4-(3,4-dichloro-phenyl)-thiazol-2-yl]-6′-fluoro-biphenyl-2-carboxylic acid (3 mg, 3%). 1H NMR (300 MHz, DMSO-d6) δ 13.18 (br s, 1H), 8.61 (d, J=1.9 Hz, 1H), 8.50 (s, 1H), 8.28-8.38 (m, 2H), 8.10 (dd, J=8.4, 2.0 Hz, 1H), 7.78 (d, J=8.5 Hz, 1H), 7.39-7.57 (m, 3H), 7.33 (d, J=9.2 Hz, 1H).

Workup

  1. customthe acid was purified

Sources & evidence

ORD record
ord-cadd2ab5a9d340628303afed053f5425
Source dataset
uspto-grants-2015_07
Patent number
US09073881B2

Reaction notes

Loading…