Cesium carbonate → 3-{4-[3-(4-Chloro-2-cyclohexyl-phenoxy)-5-methyl-phenoxy]-2-methyl-phenyl}-propionic acid

HRID 1822253

反応式

HRID 1822253 の反応式
C[O:2][C:3](=[O:22])[CH2:4][CH2:5][C:6]1[CH:11]=[CH:10][C:9]([O:12][C:13]2[CH:18]=[C:17]([CH3:19])[CH:16]=[C:15](Br)[CH:14]=2)=[CH:8][C:7]=1[CH3:21].[Cl:23][C:24]1[CH:29]=[CH:28][C:27]([OH:30])=[C:26]([CH:31]2[CH2:36][CH2:35][CH2:34][CH2:33][CH2:32]2)[CH:25]=1.CC(C)(C(=O)CC(=O)C(C)(C)C)C.C(=O)([O-])[O-].[Cs+].[Cs+].[OH-].[Na+]>CN1C(=O)CCC1.CO.[Cu]Cl>[Cl:23][C:24]1[CH:29]=[CH:28][C:27]([O:30][C:15]2[CH:14]=[C:13]([CH:18]=[C:17]([CH3:19])[CH:16]=2)[O:12][C:9]2[CH:10]=[CH:11][C:6]([CH2:5][CH2:4][C:3]([OH:2])=[O:22])=[C:7]([CH3:21])[CH:8]=2)=[C:26]([CH:31]2[CH2:36][CH2:35][CH2:34][CH2:33][CH2:32]2)[CH:25]=1

参加物

9

反応物 5

HCID 10796Cesium carbonateHCID 14798Sodium HydroxideHCID 707002,2,6,6-Tetramethyl-3,5-heptanedioneHCID 831204-Chloro-2-cyclohexylphenolHCID 578942123-[4-(3-Bromo-5-methyl-phenoxy)-2-methyl-phenyl]-propionic acid methyl ester

生成物 1

HCID 112024153-{4-[3-(4-Chloro-2-cyclohexyl-phenoxy)-5-methyl-phenoxy]-2-methyl-phenyl}-propionic acid収率 38%

試薬・触媒・溶媒 3

HCID 62652Cuprous chloride触媒HCID 887Methanol溶媒HCID 13387N-methyl-2-pyrrolidone溶媒

実験手順

A solution of 3-[4-(3-bromo-5-methyl-phenoxy)-2-methyl-phenyl]-propionic acid methyl ester (0.1 g, 0.27 mmol), 4-chloro-2-cyclohexyl-phenol (63 mg, 0.3 mmol), copper(I) chloride (13 mg, 0.13 mmol), 2,2,6,6-tetramethyl-3,5-heptanedione (0.01 mL, 0.07 mmol), and cesium carbonate (105 mg, 0.32 mmol) in NMP (3 mL) is heated to 120° C. The reaction is stirred overnight and cooled to rt. The reaction is quenched with 1N aqueous HCl and extracted with ethyl ether. The organic layer is washed with brine, dried over sodium sulfate, and filtered. The solvent is removed to afford the crude ester intermediate. The intermediate is treated with 5N NaOH (0.4 mL, 2.2 mmol) in MeOH (5 mL) and heated to reflux. The reaction stirred at reflux for 2 hours and then cooled. The reaction is quenched with 1N aqueous HCl to obtain pH=4. The aqueous layer is extracted with ethyl ether. The organic layer is washed with brine, dried over sodium sulfate, and filtered. The solvent is removed to afford the crude product. The crude is purified by HPLC to afford 49 mg (38%) of desired product. 1H NMR (400 MHz, CDCl3); MS (ES+) m/z mass calculated for C29H31ClO4 478, found 479 and 481 (M+1 and M+3, 100%).

後処理

  1. customThe reaction is quenched with 1N aqueous HCl
  2. extractionextracted with ethyl ether
  3. washThe organic layer is washed with brine
  4. dry with materialdried over sodium sulfate
  5. filtrationfiltered
  6. customThe solvent is removed
  7. customto afford the crude ester intermediate
  8. temperatureheated to reflux
  9. stirringThe reaction stirred
  10. temperatureat reflux for 2 hours
  11. temperaturecooled
  12. customThe reaction is quenched with 1N aqueous HCl
  13. customto obtain pH=4
  14. extractionThe aqueous layer is extracted with ethyl ether
  15. washThe organic layer is washed with brine
  16. dry with materialdried over sodium sulfate
  17. filtrationfiltered
  18. customThe solvent is removed
  19. customto afford the crude product
  20. customThe crude is purified by HPLC

出典と根拠

ORDレコード
ord-e510c01daf424293b294850e22a1f045
出典データセット
uspto-grants-2009_10
特許番号
US07608639B2

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