Triisopropyl borate → (5-(Cyclopropylcarbamoyl)-3-fluoro-2-methylphenyl)boronic acid

HRID 889335ノート

反応式

HRID 889335 の反応式
[CH:1]1([NH:4][C:5](=[O:15])[C:6]2[CH:11]=[C:10]([F:12])[C:9]([CH3:13])=[C:8](I)[CH:7]=2)[CH2:3][CH2:2]1.[H-].[Na+].C([Li])CCC.[B:23](OC(C)C)([O:28]C(C)C)[O:24]C(C)C>C1COCC1>[CH:1]1([NH:4][C:5]([C:6]2[CH:11]=[C:10]([F:12])[C:9]([CH3:13])=[C:8]([B:23]([OH:28])[OH:24])[CH:7]=2)=[O:15])[CH2:3][CH2:2]1

参加物

6

反応物 4

HCID 21531Triisopropyl borateHCID 24758Sodium hydrideHCID 21914570N-Cyclopropyl-3-fluoro-5-iodo-4-methylbenzamide2 回HCID 178418339Butyllithium

生成物 1

HCID 21914527(5-(Cyclopropylcarbamoyl)-3-fluoro-2-methylphenyl)boronic acid

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒

反応条件

温度
-75 °C

実験手順

N-Cyclopropyl-5-fluoro-3-iodo-4-methylbenzamide (Intermediate 37, 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.

後処理

  1. temperaturemaintaining a temperature of <−70° C
  2. customThe reaction was quenched with water (20 ml)
  3. temperatureto warm to 5° C
  4. concentrationThe reaction was concentrated under vacuum
  5. customthe residue partitioned between saturated ammonium chloride and ethyl acetate
  6. washThe organic phase was washed with saturated ammonium chloride, brine
  7. dry with materialdried (sodium sulphate)
  8. dissolutionThe residue was dissolved in DCM/ethyl acetate
  9. custompurified by column chromatography on silica eluting with an ethyl acetate/DCM gradient (5-100% ethyl acetate)
  10. customthe solvent evaporated under vacuum

出典と根拠

ORDレコード
ord-73c42481adf344dda96cac4bdad45f0e
出典データセット
uspto-grants-2012_08
特許番号
US08252818B2

反応ノート

読み込み中…