Triisopropyl borate → 3-cyano-1-cyclobutyl-6-cyclopropyl-1H-indol-2-ylboronic acid

HRID 1028004ノート

反応式

HRID 1028004 の反応式
[CH:1]1([N:6]2[C:14]3[C:9](=[CH:10][C:11](F)=[C:12]([CH3:15])[CH:13]=3)[C:8]([C:17]#[N:18])=[CH:7]2)[CH2:5][CH2:4][CH2:3]C1.[B:19](OC(C)C)([O:24]C(C)C)[O:20]C(C)C.[Li+].[CH3:33][CH:34]([N-]C(C)C)C>C1COCC1>[C:17]([C:8]1[C:9]2[C:14](=[CH:13][C:12]([CH:15]3[CH2:34][CH2:33]3)=[CH:11][CH:10]=2)[N:6]([CH:1]2[CH2:3][CH2:4][CH2:5]2)[C:7]=1[B:19]([OH:24])[OH:20])#[N:18]

参加物

5

反応物 3

HCID 21531Triisopropyl borateHCID 2724682Lithium diisopropylamideHCID 667305931-cyclopentyl-5-fluoro-6-methyl-1H-indole-3-carbonitrile

生成物 1

HCID 667305423-cyano-1-cyclobutyl-6-cyclopropyl-1H-indol-2-ylboronic acid

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒

反応条件

温度
-78 °C

実験手順

Into a solution of 1-cyclopentyl-5-fluoro-6-methyl-1H-indole-3-carbonitrile (4.4 g, 18.2 mmol) and triisopropyl borate (7.6 mL, 33 mmol) in THF (75 mL) at −78° C. was added LDA (1.5 M in cyclohexane, 15.8 mL, 23.7 mmol). The mixture was stirred at −78° C. for 30 min, quenched with ice water (200 mL) and stirred for 15 min without cooling. The mixture was extracted with ethyl acetate 1:1 in hexane (20 mL). The aqueous layer was acidified with aq. 2 N HCl to pH 5 and then extracted with CH2Cl2 (100 mL). The organic layer was dried over Na2SO4 and concentrated to give 3-cyano-1-cyclobutyl-6-cyclopropyl-1H-indol-2-ylboronic acid as a solid (6.2 g, 90% pure by LCMS) which was used in the next step without further purification.

後処理

  1. customquenched with ice water (200 mL)
  2. stirringstirred for 15 min
  3. temperaturewithout cooling
  4. extractionThe mixture was extracted with ethyl acetate 1:1 in hexane (20 mL)
  5. extractionextracted with CH2Cl2 (100 mL)
  6. dry with materialThe organic layer was dried over Na2SO4
  7. concentrationconcentrated

出典と根拠

ORDレコード
ord-fee8d33d798d46e09ba7d37b41fd15ea
出典データセット
uspto-grants-2014_05
特許番号
US08735414B2

反応ノート

読み込み中…