Potassium Carbonate → 3-Fluoro-4-(7-methoxyisoquinolin-3-yl)benzoic acid

HRID 1472698Notes

Reaction equation

HRID 1472698 reaction equation
Cl[C:2]1[N:3]=[CH:4][C:5]2[C:10]([CH:11]=1)=[CH:9][CH:8]=[C:7]([O:12][CH3:13])[CH:6]=2.[C:14]([C:17]1[CH:22]=[CH:21][C:20](B(O)O)=[C:19]([F:26])[CH:18]=1)([OH:16])=[O:15].C([O-])([O-])=O.[K+].[K+]>COCCOCCO.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]>[F:26][C:19]1[CH:18]=[C:17]([CH:22]=[CH:21][C:20]=1[C:2]1[N:3]=[CH:4][C:5]2[C:10]([CH:11]=1)=[CH:9][CH:8]=[C:7]([O:12][CH3:13])[CH:6]=2)[C:14]([OH:16])=[O:15]

Participants

7

Reactant 3

HCID 11430Potassium CarbonateHCID 231341774-(Dihydroxyboranyl)-3-fluorobenzoic acidHCID 534255653-Chloro-7-methoxyisoquinoline2×

Product 1

HCID 679748263-Fluoro-4-(7-methoxyisoquinolin-3-yl)benzoic acidYield 30.4%

Reagents, catalysts & solvents 3

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 962WaterSolventHCID 8134Diethylene Glycol Monomethyl EtherSolvent

Conditions

Temperature
120 °C

Procedure

A mixture of 3-chloro-7-methoxyisoquinoline (Intermediate 12) (300 mg, 1.55 mmol), 4-carboxy-2-fluorophenylboronic acid (285 mg, 1.55 mmol), K2CO3 (642 mg, 4.65 mmol) and Pd(dppf)Cl2 (30 mg, 0.037 mmol) in DEGME (7 mL) and water (2 mL) was stirred under N2 atmosphere at 120° C. for 3 hours. The resulting mixture was cooled to room temperature and filtered. The filtrate was acidified with aqueous HCl (2M) until pH=6 and filtered. The solid was dried under reduced pressure to give 3-fluoro-4-(7-methoxyisoquinolin-3-yl)benzoic acid (140 mg, yield: 30%) as off-white solid.

Workup

  1. temperatureThe resulting mixture was cooled to room temperature
  2. filtrationfiltered
  3. filtrationfiltered
  4. customThe solid was dried under reduced pressure

Sources & evidence

ORD record
ord-8af4442cfb8d45bababeec4ebcf03b6f
Source dataset
uspto-grants-2015_04
Patent number
US09012646B2

Reaction notes

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