Potassium Carbonate → 3-Chloro-4-(6-methoxyquinolin-2-yl)benzoic acid

HRID 1507336

Reaction equation

Cl[C:2]1[CH:11]=[CH:10][C:9]2[C:4](=[CH:5][CH:6]=[C:7]([O:12][CH3:13])[CH:8]=2)[N:3]=1.[C:14]([C:17]1[CH:22]=[CH:21][C:20](B(O)O)=[C:19]([Cl:26])[CH:18]=1)([OH:16])=[O:15].C([O-])([O-])=O.[K+].[K+]>COCCOCCO.O.CCOC(C)=O.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[Cl:26][C:19]1[CH:18]=[C:17]([CH:22]=[CH:21][C:20]=1[C:2]1[CH:11]=[CH:10][C:9]2[C:4](=[CH:5][CH:6]=[C:7]([O:12][CH3:13])[CH:8]=2)[N:3]=1)[C:14]([OH:16])=[O:15]

Participants

Conditions

Temperature: 110 °C

Procedure

A mixture of 2-chloro-6-methoxyquinoline (Intermediate 1) (200 mg, 1.04 mmol), 4-carboxy-2-chlorophenylboronic acid (247 mg, 1.24 mmol) and K2CO3 (369 mg, 2.70 mmol) in DEGME/H2O (7.0 mL/2.0 mL) was degassed three times under N2 atmosphere. Then PdCl2(dppf) (75 mg, 0.104 mmol) was added and the mixture was heated to 110° C. for 3 hours under N2 atmosphere. The reaction mixture was diluted with EtOAc (100 mL) and filtered. The filtrate was washed with brine (20 mL), dried over Na2SO4, filtered and concentrated to give 3-chloro-4-(6-methoxyquinolin-2-yl)benzoic acid (150 mg, yield 46%) as a yellow solid, which was used for the next step without further purification.

Workup

customwas degassed three times under N2 atmosphere
filtrationfiltered
washThe filtrate was washed with brine (20 mL)
dry with materialdried over Na2SO4
filtrationfiltered
concentrationconcentrated

Sources & evidence

ORD record: ord-df7c9789f2b44148bb50685ac05817e7
Source dataset: uspto-grants-2015_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09221810B2

Linked notes

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