반응 #59708

반응 방정식

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

용매

THF

반응 조건

후처리

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

실험 절차

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.

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