Reaktion #304096

Reaktionsgleichung

(S)-tert-Butyl 4-(1-amino-3-(4-iodophenyl)-1-oxopropan-2-ylcarbamoyl)tetrahydro-2H-pyran-4-ylcarbamate

4-fluorophenylboronic acid

4-(isopropylsulfonyl)phenylboronic acid

potassium carbonate

→

(S)-tert-butyl 4-(1-amino-3-(4′-fluorobiphenyl-4-yl)-1-oxopropan-2-ylcarbamoyl)tetrahydro-2H-pyran-4-ylcarbamate

(S)-tert-butyl 4-(1-amino-3-(4′-(isopropylsulfonyl)biphenyl-4-yl)-1-oxopropan-2-ylcarbamoyl)tetrahydro-2H-pyran-4-ylcarbamate

Lösungsmittel

acetonitrile

Reaktionsbedingungen

Aufarbeitung

1. 1
   SonstigeThe reaction was evaporated
2. 2
   workup.DISSOLUTIONdissolved in dichloromethane
3. 3
   Sonstigeabsorbed onto silica
4. 4
   Sonstigeto purified by chromatography on silica eluting with 50% ethyl acetate in isohexane

Vorschrift

(S)-tert-Butyl 4-(1-amino-3-(4-iodophenyl)-1-oxopropan-2-ylcarbamoyl)tetrahydro-2H-pyran-4-ylcarbamate (Example 1, step (iii), 1.0 g) in acetonitrile (5 mL) under nitrogen was treated with 4-fluorophenylboronic acid (0.135 g) and 4-(isopropylsulfonyl)phenylboronic acid (0.220 g) followed by aqueous potassium carbonate (2M, 1.93 mL) and 1,1 bis(di-tert-butylphosphino)ferrocene palladium dichloride (13 mg). The mixture was stirred at 75° C. for 18 h. The reaction was evaporated, dissolved in dichloromethane, absorbed onto silica and to purified by chromatography on silica eluting with 50% ethyl acetate in isohexane and then 100% ethyl acetate to afford (S)-tert-butyl 4-(1-amino-3-(4′-fluorobiphenyl-4-yl)-1-oxopropan-2-ylcarbamoyl)tetrahydro-2H-pyran-4-ylcarbamate and (S)-tert-butyl 4-(1-amino-3-(4′-(isopropylsulfonyl)biphenyl-4-yl)-1-oxopropan-2-ylcarbamoyl)tetrahydro-2H-pyran-4-ylcarbamate as a mixture (0.620 g).

Quelle