反应 #59708

反应方程式

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

溶剂

THF

反应条件

后处理

1. 1
   温度maintaining a temperature of ←70° C
2. 2
   其他The reaction was quenched with water (20 ml)
3. 3
   温度to warm to 5° C
4. 4
   浓缩The reaction was concentrated under vacuum
5. 5
   其他the residue partitioned between saturated ammonium chloride and ethyl acetate
6. 6
   洗涤The organic phase was washed with saturated ammonium chloride, brine
7. 7
   干燥dried (sodium sulphate)
8. 8
   workup.DISSOLUTIONThe residue was dissolved in DCM/ethyl acetate
9. 9
   其他purified by column chromatography on silica eluting with an ethyl acetate/DCM gradient (5-100% ethyl acetate)
10. 10
    其他the solvent evaporated under vacuum

实验过程

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.

来源