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

HRID 1472699

반응식

HRID 1472699 반응식
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

참가 물질

8

반응물 4

HCID 962WaterHCID 11430Potassium CarbonateHCID 3121834-Carboxyphenylboronic AcidHCID 86698074HCID 86698074, 화합물2회

생성물 1

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

시약·촉매·용매 3

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)촉매HCID 8857Ethyl Acetate용매HCID 49835946Degme H2O용매

반응 조건

온도
120 °C

실험 절차

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%).

후처리

  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

출처 및 근거

ORD 기록
ord-2c8ae20877284d7d8e763803ed63b51f
출처 데이터셋
uspto-grants-2015_04
특허 번호
US09012646B2

연결된 노트

불러오는 중…