Sodium Carbonate → (1S,2R)-4'-(2-Hydroxy-1-methyl-4-pyridin-3-yl-butoxy)-3-methyl-biphenyl-4-carbonitrile

HRID 379998

Reaktionsgleichung

Reaktionsgleichung von HRID 379998
[OH:1][C@H:2]([CH2:15][CH2:16][C:17]1[CH:18]=[N:19][CH:20]=[CH:21][CH:22]=1)[C@H:3]([CH3:14])[O:4][C:5]1[CH:10]=[CH:9][C:8](B(O)O)=[CH:7][CH:6]=1.Br[C:24]1[CH:31]=[CH:30][C:27]([C:28]#[N:29])=[C:26]([CH3:32])[CH:25]=1.C(=O)([O-])[O-].[Na+].[Na+]>C(O)C.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[OH:1][C@H:2]([CH2:15][CH2:16][C:17]1[CH:18]=[N:19][CH:20]=[CH:21][CH:22]=1)[C@H:3]([CH3:14])[O:4][C:5]1[CH:10]=[CH:9][C:8]([C:24]2[CH:31]=[CH:30][C:27]([C:28]#[N:29])=[C:26]([CH3:32])[CH:25]=2)=[CH:7][CH:6]=1

Komponenten

6

Edukt 3

HCID 10340Sodium CarbonateHCID 1442674-Bromo-2-methylbenzonitrileHCID 54413593(1S,2R)-4-(2-hydroxy-1-methyl-4-pyridin-3-ylbutoxy)benzeneboronic acid

Produkt 1

HCID 54342631(1S,2R)-4'-(2-Hydroxy-1-methyl-4-pyridin-3-yl-butoxy)-3-methyl-biphenyl-4-carbonitrileAusbeute 59,3 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 178418397HCID 178418397, VerbindungKatalysatorHCID 702EthanolLösungsmittel

Reaktionsbedingungen

Temperatur
90 °C

Versuchsvorschrift

Prepared according to the method described in Example 12b) from (1S,2R)-4-(2-hydroxy-1-methyl-4-pyridin-3-ylbutoxy)benzeneboronic acid (0.150 g, Example 33), 4-bromo-2-methylbenzonitrile (0.301 g), 2M aqueous sodium carbonate (0.50 ml) and tetrakis(triphenylphosphine)palladium (0) (0.025 g) in ethanol (3 ml). The reaction mixture was heated at 90° C. for 4 hours. After cooling, the solution was concentrated under reduced pressure, taken up in ethanol and concentrated again (twice). The residue was triturated with acetone and then filtered through silica gel. The filtrate was concentrated under reduced pressure, dissolved in dichloromethane, filtered and purified by normal-phase HPLC eluting with a gradient of 0-25% ethanol in dichloromethane to give an oil which crystallised under high vacuum over 24 hours. Trituration with diethyl ether resulted in isolation of the title compound as a solid (0.11 g).

Aufarbeitung

  1. customPrepared
  2. temperatureAfter cooling
  3. concentrationthe solution was concentrated under reduced pressure
  4. concentrationconcentrated again (twice)
  5. customThe residue was triturated with acetone
  6. filtrationfiltered through silica gel
  7. concentrationThe filtrate was concentrated under reduced pressure
  8. dissolutiondissolved in dichloromethane
  9. filtrationfiltered
  10. custompurified by normal-phase HPLC
  11. washeluting with a gradient of 0-25% ethanol in dichloromethane
  12. customto give an oil which
  13. customcrystallised under high vacuum over 24 hours

Quellen und Nachweise

ORD-Eintrag
ord-eec65aebaf8e42598c408b47698a6b57
Quelldatensatz
uspto-grants-2001_10
Patentnummer
US06300352B1

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