Chlorophene → 3-{4-[3-(2-Benzyl-4-chloro-phenoxy)-phenoxy]-2-methyl-phenyl}-propionic acid

HRID 1822252

Reaktionsgleichung

Reaktionsgleichung von HRID 1822252
C[O:2][C:3](=[O:21])[CH2:4][CH2:5][C:6]1[CH:11]=[CH:10][C:9]([O:12][C:13]2[CH:18]=[CH:17][CH:16]=[C:15](Br)[CH:14]=2)=[CH:8][C:7]=1[CH3:20].[CH2:22]([C:29]1[CH:34]=[C:33]([Cl:35])[CH:32]=[CH:31][C:30]=1[OH:36])[C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=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>[CH2:22]([C:29]1[CH:34]=[C:33]([Cl:35])[CH:32]=[CH:31][C:30]=1[O:36][C:15]1[CH:14]=[C:13]([CH:18]=[CH:17][CH:16]=1)[O:12][C:9]1[CH:10]=[CH:11][C:6]([CH2:5][CH2:4][C:3]([OH:2])=[O:21])=[C:7]([CH3:20])[CH:8]=1)[C:23]1[CH:24]=[CH:25][CH:26]=[CH:27][CH:28]=1

Komponenten

9

Edukt 5

HCID 8425ChloropheneHCID 10796Cesium carbonateHCID 14798Sodium HydroxideHCID 707002,2,6,6-Tetramethyl-3,5-heptanedioneHCID 578941923-[4-(3-Bromo-phenoxy)-2-methyl-phenyl]-propionic acid methyl ester

Produkt 1

HCID 112022663-{4-[3-(2-Benzyl-4-chloro-phenoxy)-phenoxy]-2-methyl-phenyl}-propionic acidAusbeute 47 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 62652Cuprous chlorideKatalysatorHCID 887MethanolLösungsmittelHCID 13387N-methyl-2-pyrrolidoneLösungsmittel

Versuchsvorschrift

A solution of 3-[4-(3-bromo-phenoxy)-2-methyl-phenyl]-propionic acid methyl ester (0.1 g, 0.3 mmol), 2-benzyl-4-chloro-phenol (69 mg, 0.32 mmol), copper(I) chloride (14 mg, 0.14 mmol), 2,2,6,6-tetramethyl-3,5-heptanedione (0.01 mL, 0.07 mmol), and cesium carbonate (113 mg, 0.35 mmol) in NMP (3 mL) is heated to 120° C. The reaction is stirred overnight and cooled to rt. The reaction is then quenched with 1N aqueous HCl and extracted with ethyl ether. The organic 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 is 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 prep HPLC to afford 63 mg (47%) of desired product. 1H NMR (400 MHz, CDCl3); MS (ES+) m/z mass calculated for C29H25ClO4 472, found 473 and 475 (M+1 and M+3, 100%).

Aufarbeitung

  1. customThe reaction is then quenched with 1N aqueous HCl
  2. extractionextracted with ethyl ether
  3. washThe organic 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 is 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 prep HPLC

Quellen und Nachweise

ORD-Eintrag
ord-79db57fa3e86449592fdd8901ca58687
Quelldatensatz
uspto-grants-2009_10
Patentnummer
US07608639B2

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