Hydrochloric Acid → {3-[4-(5-Cyclopropylisoxazol-4-yl)benzyl]-4-difluoromethoxy-2-ethyl-8-fluoroquinolin-5-yloxy}acetic acid methyl ester

HRID 1922129노트

반응식

HRID 1922129 반응식
[F:1][CH:2]([F:33])[O:3][C:4]1[C:13]2[C:8](=[C:9]([F:20])[CH:10]=[CH:11][C:12]=2[O:14][CH2:15][C:16]([O:18][CH3:19])=[O:17])[N:7]=[C:6]([CH2:21][CH3:22])[C:5]=1[CH2:23][C:24]1[CH:29]=[CH:28][C:27](B(O)O)=[CH:26][CH:25]=1.Br[C:35]1[CH:36]=[N:37][O:38][C:39]=1[CH:40]1[CH2:42][CH2:41]1.C(=O)([O-])O.[Na+].Cl>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].COCCOC>[CH3:19][O:18][C:16](=[O:17])[CH2:15][O:14][C:12]1[CH:11]=[CH:10][C:9]([F:20])=[C:8]2[C:13]=1[C:4]([O:3][CH:2]([F:33])[F:1])=[C:5]([CH2:23][C:24]1[CH:29]=[CH:28][C:27]([C:35]3[CH:36]=[N:37][O:38][C:39]=3[CH:40]3[CH2:42][CH2:41]3)=[CH:26][CH:25]=1)[C:6]([CH2:21][CH3:22])=[N:7]2

참가 물질

8

반응물 4

HCID 313Hydrochloric AcidHCID 516892Sodium BicarbonateHCID 674575914-Bromo-5-cyclopropylisoxazoleHCID 67458287(4-{[4-Difluoromethoxy-2-ethyl-8-fluoro-5-(2-methoxy-2-oxoethoxy) quinolin-3-yl]methyl}phenyl)boronic acid

생성물 1

HCID 67458143{3-[4-(5-Cyclopropylisoxazol-4-yl)benzyl]-4-difluoromethoxy-2-ethyl-8-fluoroquinolin-5-yloxy}acetic acid methyl ester수율 17.6%

시약·촉매·용매 3

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)촉매HCID 962Water용매2회HCID 80711,2-Dimethoxyethane용매

반응 조건

온도
85 °C

실험 절차

A mixture of (4-{[4-difluoromethoxy-2-ethyl-8-fluoro-5-(2-methoxy-2-oxoethoxy)quinolin-3-yl]methyl}phenyl)boronic acid (0.15 g), 4-bromo-5-cyclopropylisoxazole (0.24 g), [1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium (0.027 g), sodium hydrogen carbonate (0.082 g), 1,2-dimethoxyethane (1.0 mL) and water (0.4 mL) was heated at 85° C. for 2 hours. The mixture was cooled to room temperature, diluted with water (5 mL), neutralised by the addition of 1.0 M aqueous hydrochloric acid solution (1.0 mL) and extracted with ethyl acetate. The combined extracts were washed with saturated aqueous sodium chloride solution, dried over magnesium sulphate and then concentrated under reduced pressure. Purification of the residue by column chromatography on silica gel, eluting with a mixture of cyclohexane and ethyl acetate (1:0 to 7:3 by volume) gave title compound as a colourless oil (0.03 g).

후처리

  1. temperatureThe mixture was cooled to room temperature
  2. extractionextracted with ethyl acetate
  3. washThe combined extracts were washed with saturated aqueous sodium chloride solution
  4. dry with materialdried over magnesium sulphate
  5. concentrationconcentrated under reduced pressure
  6. customPurification of the residue by column chromatography on silica gel
  7. washeluting with a mixture of cyclohexane and ethyl acetate (1:0 to 7:3 by volume)

출처 및 근거

ORD 기록
ord-86f7f5ac01794e98badd5bfdbdb08304
출처 데이터셋
uspto-grants-2012_05
특허 번호
US08173812B2

반응 노트

불러오는 중…