Potassium Carbonate → 3-(4',5'-Difluoro-2'-methoxybiphenyl-4-yloxymethyl)-4-fluorobenzoic acid methyl ester

HRID 1665241노트

반응식

HRID 1665241 반응식
[CH3:1][O:2][C:3](=[O:20])[C:4]1[CH:9]=[CH:8][C:7]([F:10])=[C:6]([CH2:11][O:12][C:13]2[CH:18]=[CH:17][C:16](I)=[CH:15][CH:14]=2)[CH:5]=1.[F:21][C:22]1[C:27]([F:28])=[CH:26][C:25](B(O)O)=[C:24]([O:32][CH3:33])[CH:23]=1.C(=O)([O-])[O-].[K+].[K+]>CN(C=O)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]>[CH3:1][O:2][C:3](=[O:20])[C:4]1[CH:9]=[CH:8][C:7]([F:10])=[C:6]([CH2:11][O:12][C:13]2[CH:18]=[CH:17][C:16]([C:25]3[CH:26]=[C:27]([F:28])[C:22]([F:21])=[CH:23][C:24]=3[O:32][CH3:33])=[CH:15][CH:14]=2)[CH:5]=1

참가 물질

7

반응물 3

HCID 11430Potassium CarbonateHCID 16217679(4,5-Difluoro-2-methoxyphenyl)boronic acidHCID 671503534-Fluoro-3-(4-iodophenoxy)methylbenzoic acid methyl ester

생성물 1

HCID 671503573-(4',5'-Difluoro-2'-methoxybiphenyl-4-yloxymethyl)-4-fluorobenzoic acid methyl ester수율 67%

시약·촉매·용매 3

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)촉매HCID 962Water용매HCID 6228Dimethylformamide용매

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온도
45 °C

실험 절차

To a mixture of 4-fluoro-3-(4-iodophenoxy)methylbenzoic acid methyl ester (1.1 g, 2.85 mmol) and 4,5-difluoro-2-methoxyphenylboronic acid (0.642 g, 3.4 mmol) in DMF (15 mL) and water (2.5 mL) was added Pd(dppf)Cl2 (220 mg, 0.27 mmol) and potassium carbonate (1.24 g, 9.0 mmol). The mixture was stirred at 45° C. overnight and solvents were evaporated. The residue was extracted with ethyl acetate and water. The organic layer was dried and concentrated. The residue was purified through flash column chromatography (120 g silica gel, 5% to 40% ethyl acetate in hexanes over 25 minutes) to give a white solid as 3-(4′,5′-difluoro-2′-methoxybiphenyl-4-yloxymethyl)-4-fluorobenzoic acid methyl ester (0.76 g, 67%).

후처리

  1. customsolvents were evaporated
  2. extractionThe residue was extracted with ethyl acetate and water
  3. customThe organic layer was dried
  4. concentrationconcentrated
  5. customThe residue was purified through flash column chromatography (120 g silica gel, 5% to 40% ethyl acetate in hexanes over 25 minutes)

출처 및 근거

ORD 기록
ord-63e2b9ac7335416a8d92a5de3f607588
출처 데이터셋
uspto-grants-2011_10
특허 번호
US08039495B2

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