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

HRID 1922088ノート

反応式

HRID 1922088 の反応式
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

参加物

7

反応物 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

生成物 1

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

試薬・触媒・溶媒 2

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

反応条件

温度
90 °C

実験手順

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 2.0 M 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 1.0 M 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 0.1 M 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).

後処理

  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 0.1 M 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

出典と根拠

ORDレコード
ord-c3b6190817f6401d8651c59f077d4632
出典データセット
uspto-grants-2012_05
特許番号
US08173812B2

反応ノート

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