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

HRID 1627672

反応式

HRID 1627672 の反応式
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

参加物

8

反応物 4

HCID 962WaterHCID 11430Potassium CarbonateHCID 3121834-Carboxyphenylboronic AcidHCID 86698074HCID 86698074、化合物2 回

生成物 1

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

試薬・触媒・溶媒 3

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)触媒HCID 8857Ethyl Acetate溶媒HCID 49835946Degme H2O溶媒

反応条件

温度
120 °C

実験手順

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%).

後処理

  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

出典と根拠

ORDレコード
ord-0927221d98744ba79ebff8f4cdbd67aa
出典データセット
uspto-grants-2014_07
特許番号
US08785643B2

関連ノート

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