1(2H)-Isoquinolinone → 2-(4-fluorobenzyl)isoquinolin-1(2H)-one

HRID 1948211

反応式

HRID 1948211 の反応式
C[Si]([N-][Si](C)(C)C)(C)C.[Na+].[C:11]1(=[O:21])[C:20]2[C:15](=[CH:16][CH:17]=[CH:18][CH:19]=2)[CH:14]=[CH:13][NH:12]1.Br[CH2:23][C:24]1[CH:29]=[CH:28][C:27]([F:30])=[CH:26][CH:25]=1>C1COCC1.CN(C=O)C>[F:30][C:27]1[CH:28]=[CH:29][C:24]([CH2:23][N:12]2[CH:13]=[CH:14][C:15]3[C:20](=[CH:19][CH:18]=[CH:17][CH:16]=3)[C:11]2=[O:21])=[CH:25][CH:26]=1

参加物

6

反応物 3

HCID 102841(2H)-IsoquinolinoneHCID 680214-Fluorobenzyl bromideHCID 2724254Sodium bis(trimethylsilyl)amide

生成物 1

HCID 93544452-(4-fluorobenzyl)isoquinolin-1(2H)-one収率 74%

試薬・触媒・溶媒 2

HCID 6228Dimethylformamide溶媒HCID 8028Tetrahydrofuran溶媒2 回

反応条件

温度
0 °C

実験手順

According to Scheme 11: To a solution of NaHMDS (2 eq, 3.00 mmol, 0.50 g) in THF (3 mL) at 0° C. was added isoquinolin-1(2H)-one (1 eq, 1.00 mmol, 0.20 g) dissolved in THF (3 mL) and DMF (5 mL). The reaction mixture was stirred for 10 min at 0° C. then cooled at −70° C. The 1-(bromomethyl)-4-fluorobenzene (4 eq, 4.00 mmol, 0.80 g) was added in one portion to the reaction mixture. The reaction mixture was allowed to warm to room temperature, for one hour. Upon completion the reaction mixture was concentrated under vacuum and the crude residue partitioned between water and AcOEt, the aqueous layer was extracted with AcOEt. The combined organic layers were successively washed with water (2.30 mL), HCl (1M, 2.30 mL), brine (2.20 mL), dried over Na2SO4, filtered and evaporated to afford a yellow oil. The crude compound was purified on silica gel using cyclohexane/AcOEt 80/20 as eluent to afford 2-(4-fluorobenzyl)isoquinolin-1(2H)-one as a white solid (0.70 mmol, 0.26 g, 74%).

後処理

  1. temperaturethen cooled at −70° C
  2. temperatureto warm to room temperature, for one hour
  3. concentrationUpon completion the reaction mixture was concentrated under vacuum
  4. customthe crude residue partitioned between water and AcOEt
  5. extractionthe aqueous layer was extracted with AcOEt
  6. washThe combined organic layers were successively washed with water (2.30 mL), HCl (1M, 2.30 mL), brine (2.20 mL)
  7. dry with materialdried over Na2SO4
  8. filtrationfiltered
  9. customevaporated
  10. customto afford a yellow oil
  11. customThe crude compound was purified on silica gel

出典と根拠

ORDレコード
ord-c139dc6613d6422ea6322b40f4a1c733
出典データセット
uspto-grants-2013_03
特許番号
US08399493B2

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