Cesium carbonate → [4-Difluoromethoxy-2-ethyl-8-fluoro-3-(4-thiazol-2-ylbenzyl)quinolin-5-yloxy]acetic acid

HRID 1944299노트

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HRID 1944299 반응식
C[O:2][C:3](=[O:39])[CH2:4][O:5][C:6]1[CH:15]=[CH:14][C:13]([F:16])=[C:12]2[C:7]=1[C:8]([O:35][CH:36]([F:38])[F:37])=[C:9]([CH2:19][C:20]1[CH:25]=[CH:24][C:23](B3OC(C)(C)C(C)(C)O3)=[CH:22][CH:21]=1)[C:10]([CH2:17][CH3:18])=[N:11]2.Br[C:41]1[S:42][CH:43]=[CH:44][N:45]=1.O1CCOCC1.C(=O)([O-])[O-].[Cs+].[Cs+]>C(OCC)(=O)C.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]>[F:37][CH:36]([F:38])[O:35][C:8]1[C:7]2[C:12](=[C:13]([F:16])[CH:14]=[CH:15][C:6]=2[O:5][CH2:4][C:3]([OH:2])=[O:39])[N:11]=[C:10]([CH2:17][CH3:18])[C:9]=1[CH2:19][C:20]1[CH:21]=[CH:22][C:23]([C:41]2[S:42][CH:43]=[CH:44][N:45]=2)=[CH:24][CH:25]=1

참가 물질

7

반응물 4

HCID 10796Cesium carbonateHCID 312751,4-DioxaneHCID 764302-BromothiazoleHCID 67458783{4-Difluoromethoxy-2-ethyl-8-fluoro-3-[4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)benzyl]quinolin-5-yloxy}acetic acid methyl ester

생성물 1

HCID 25095818[4-Difluoromethoxy-2-ethyl-8-fluoro-3-(4-thiazol-2-ylbenzyl)quinolin-5-yloxy]acetic acid수율 42.9%

시약·촉매·용매 2

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

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온도
90 °C

실험 절차

A mixture of {4-difluoromethoxy-2-ethyl-8-fluoro-3-[4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)benzyl]quinolin-5-yloxy}acetic acid methyl ester (0.052 g), 2-bromothiazole (0.076 g), [1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium (0.060 g), 1,4-dioxane (2.0 mL) and 2.0M aqueous cesium carbonate solution (0.19 mL) was heated at 90° C. overnight. The mixture was cooled to room temperature, diluted with ethyl acetate and filtered. The filtrate was concentrated under reduced pressure, and the residue dissolved in tetrahydrofuran (5.0 mL) and 1.0M aqueous lithium hydroxide solution (0.19 mL), and the resulting mixture was stirred at room temperature for 1 hour. The mixture was concentrate to low bulk under reduced pressure, and the residue acidified by the addition 0.1M aqueous hydrochloric acid solution and then extracted with ethyl acetate. The combined extracts were dried over magnesium sulfate and then concentrated under reduced pressure. Purification of the residue by column chromatography on C-18 column gave title compound (0.020 g).

후처리

  1. temperatureThe mixture was cooled to room temperature
  2. filtrationfiltered
  3. concentrationThe filtrate was concentrated under reduced pressure
  4. dissolutionthe residue dissolved in tetrahydrofuran (5.0 mL)
  5. concentrationThe mixture was concentrate to low bulk under reduced pressure
  6. additionthe residue acidified by the addition 0.1M aqueous hydrochloric acid solution
  7. extractionextracted with ethyl acetate
  8. dry with materialThe combined extracts were dried over magnesium sulfate
  9. concentrationconcentrated under reduced pressure
  10. customPurification of the residue by column chromatography on C-18 column

출처 및 근거

ORD 기록
ord-8949485628a54b5aa6db3c0a0be8f8a6
출처 데이터셋
uspto-grants-2013_03
특허 번호
US08394830B2

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