Reaktion #59708

Reaktionsgleichung

n-butyl lithium

N-Cyclopropyl-5-fluoro-3-iodo-4-methylbenzamide

Intermediate 48

N-Cyclopropyl-5-fluoro-3-iodo-4-methylbenzamide

Triisopropyl borate

sodium hydride

→

{5-[(cyclopropylamino)carbonyl]-3-fluoro-2-methylphenyl}boronic acid

Lösungsmittel

THF

Reaktionsbedingungen

Aufarbeitung

1. 1
   Temperaturmaintaining a temperature of ←70° C
2. 2
   SonstigeThe reaction was quenched with water (20 ml)
3. 3
   Temperaturto warm to 5° C
4. 4
   EinengenThe reaction was concentrated under vacuum
5. 5
   Sonstigethe residue partitioned between saturated ammonium chloride and ethyl acetate
6. 6
   WaschenThe organic phase was washed with saturated ammonium chloride, brine
7. 7
   Trocknendried (sodium sulphate)
8. 8
   workup.DISSOLUTIONThe residue was dissolved in DCM/ethyl acetate
9. 9
   Sonstigepurified by column chromatography on silica eluting with an ethyl acetate/DCM gradient (5-100% ethyl acetate)
10. 10
    Sonstigethe solvent evaporated under vacuum

Vorschrift

N-Cyclopropyl-5-fluoro-3-iodo-4-methylbenzamide (Intermediate 48) (5 g) in THF (75 ml) was cooled to 0° C. and sodium hydride (60%, 1.23 g) added portionwise over 10 minutes. Once effervescence had ceased the reaction was cooled to −75° C. and n-butyl lithium (1.6M in hexanes, 20 ml) added over 25 minutes maintaining a temperature of ←70° C. Triisopropyl borate (8 ml) was added to the reaction over 10 minutes and the reaction stirred at −70° C. for 4 hours. The reaction was quenched with water (20 ml) and the mixture allowed to warm to 5° C. The reaction was concentrated under vacuum and the residue partitioned between saturated ammonium chloride and ethyl acetate. The organic phase was washed with saturated ammonium chloride, brine, dried (sodium sulphate) and reduced to dryness under vacuum. The residue was dissolved in DCM/ethyl acetate and purified by column chromatography on silica eluting with an ethyl acetate/DCM gradient (5-100% ethyl acetate) and then methanol. The product fractions were combined and the solvent evaporated under vacuum to give {5-[(cyclopropylamino)carbonyl]-3-fluoro-2-methylphenyl}boronic acid. LCMS MH+ 238, retention time 2.19 min.

Quelle