Water → 4-(7-Methoxy-4-methylisoquinolin-3-yl)benzoic acid

HRID 1507395

Reaction equation

HRID 1507395 reaction equation
Cl[C:2]1[N:3]=[CH:4][C:5]2[C:10]([C:11]=1[CH3:12])=[CH:9][CH:8]=[C:7]([O:13][CH3:14])[CH:6]=2.[C:15]([C:18]1[CH:23]=[CH:22][C:21](B(O)O)=[CH:20][CH:19]=1)([OH:17])=[O:16].C([O-])([O-])=O.[K+].[K+].O>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].CCOC(C)=O>[CH3:14][O:13][C:7]1[CH:6]=[C:5]2[C:10]([C:11]([CH3:12])=[C:2]([C:21]3[CH:22]=[CH:23][C:18]([C:15]([OH:17])=[O:16])=[CH:19][CH:20]=3)[N:3]=[CH:4]2)=[CH:9][CH:8]=1

Participants

8

Reactant 4

HCID 962WaterHCID 11430Potassium CarbonateHCID 3121834-Carboxyphenylboronic AcidHCID 866980743-Chloro-7-methoxy-4-methylisoquinoline2×

Product 1

HCID 679748914-(7-Methoxy-4-methylisoquinolin-3-yl)benzoic acidYield 13%

Reagents, catalysts & solvents 3

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 8857Ethyl AcetateSolventHCID 49835946Degme H2OSolvent

Conditions

Temperature
120 °C

Procedure

To a mixture of 3-chloro-7-methoxy-4-methylisoquinoline (Intermediate 15) (470 mg, 2.27 mmol), 4-carboxyphenylboronic acid (451 mg, 2.72 mmol) and K2CO3 (627 mg, 4.54 mmol) in DEGME/H2O (7 mL/1 mL) was added Pd(dppf)Cl2 (40.8 mg, 0.050 mmol) under N2 atmosphere. Then the mixture was heated to 120° C. for 16 hours. H2O (30 mL) was added, and the resulting mixture was extracted with EtOAc (15 mL×2). The aqueous layer was neutralized with 1N aqueous HCl to pH=7, extracted with EtOAc (20 mL×3). The combined organic layers were washed with H2O (20 mL) and brine (20 mL), dried over anhydrous Na2SO4, filtered and concentrated. Purification by silica gel column (PE/EtOAc=20/1 to 1/1, then EtOAc) gave 4-(7-methoxy-4-methylisoquinolin-3-yl)benzoic acid (85.0 mg, yield 13%).

Workup

  1. extractionthe resulting mixture was extracted with EtOAc (15 mL×2)
  2. extractionextracted with EtOAc (20 mL×3)
  3. washThe combined organic layers were washed with H2O (20 mL) and brine (20 mL)
  4. dry with materialdried over anhydrous Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customPurification by silica gel column (PE/EtOAc=20/1 to 1/1

Sources & evidence

ORD record
ord-b027c15b728f41e2a1f9fc5fc70d1dda
Source dataset
uspto-grants-2015_12
Patent number
US09221810B2

Linked notes

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