Potassium Phosphate, Tribasic → 1-{3,5-difluoro-4-[(phenylmethyl)oxy]phenyl}-4-[(phenylmethyl)oxy]-1H-indole

HRID 2421246

Reaktionsgleichung

Reaktionsgleichung von HRID 2421246
[C:1]1([CH2:7][O:8][C:9]2[CH:17]=[CH:16][CH:15]=[C:14]3[C:10]=2[CH:11]=[CH:12][NH:13]3)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[C:18]1([CH2:24][O:25][C:26]2[C:31]([F:32])=[CH:30][C:29](Br)=[CH:28][C:27]=2[F:34])[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1.[O-]P([O-])([O-])=O.[K+].[K+].[K+].N1CCC[C@H]1C(O)=O>CN(C=O)C>[F:32][C:31]1[CH:30]=[C:29]([N:13]2[C:14]3[C:10](=[C:9]([O:8][CH2:7][C:1]4[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=4)[CH:17]=[CH:16][CH:15]=3)[CH:11]=[CH:12]2)[CH:28]=[C:27]([F:34])[C:26]=1[O:25][CH2:24][C:18]1[CH:19]=[CH:20][CH:21]=[CH:22][CH:23]=1

Komponenten

6

Edukt 4

HCID 62657Potassium Phosphate, TribasicHCID 884654-(phenylmethoxy)-1H-indoleHCID 145742L-ProlineHCID 142076414-Bromo-2,6-difluoro-1-(benzyloxy)benzene

Produkt 1

HCID 596279281-{3,5-difluoro-4-[(phenylmethyl)oxy]phenyl}-4-[(phenylmethyl)oxy]-1H-indole

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6228DimethylformamideLösungsmittel

Reaktionsbedingungen

Temperatur
140 °C

Versuchsvorschrift

4-[(phenylmethyl)oxy]-1H-indole (500 mg, 2.24 mmoL), 4-bromo-2,6-difluorophenyl phenylmethyl ether (prepared as described in part a), 559 mg, 1.87 mmoL), K3PO4 (990 mg, 4.67 mmoL) and L-Proline (43 mg, 0.373 mmoL) were dissolved in DMF (5 mL) in a microwave vial and degassed by sonication under a flow of argon. To this was added CuI (71 mg, 0.373 mmoL) and the solution was heated to 140° C. in the microwave reactor. After 3 hours the mixture was partitioned between ethyl acetate (100 mL)/water (100 mL), the phases were separated and the aqueous phase re-extracted with ethyl acetate (100 mL). The combined organic phases were washed with sat. NH4Cl (2×100 mL), water (100 mL) and brine (2×100 mL) and finally dried over MgSO4. The crude product was purified by flash chromatography (Biotage SP4, 40+S Cartridge) eluting with a gradient of 0 to 20% Et2O in hexane to give the title compound (D21), (299 mg).

Aufarbeitung

  1. customdegassed by sonication under a flow of argon
  2. additionTo this was added CuI (71 mg, 0.373 mmoL)
  3. customAfter 3 hours the mixture was partitioned between ethyl acetate (100 mL)/water (100 mL)
  4. customthe phases were separated
  5. extractionthe aqueous phase re-extracted with ethyl acetate (100 mL)
  6. washThe combined organic phases were washed with sat. NH4Cl (2×100 mL), water (100 mL) and brine (2×100 mL)
  7. dry with materialfinally dried over MgSO4
  8. customThe crude product was purified by flash chromatography (Biotage SP4, 40+S Cartridge)
  9. washeluting with a gradient of 0 to 20% Et2O in hexane

Quellen und Nachweise

ORD-Eintrag
ord-21b4da8f52ec452fbd78b8ee88eef7e4
Quelldatensatz
uspto-grants-2011_06
Patentnummer
US07956083B2

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