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

HRID 1948211

반응식

HRID 1948211 반응식
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

참가 물질

6

반응물 3

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

생성물 1

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

시약·촉매·용매 2

HCID 6228Dimethylformamide용매HCID 8028Tetrahydrofuran용매2회

반응 조건

온도
0 °C

실험 절차

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%).

후처리

  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

출처 및 근거

ORD 기록
ord-c139dc6613d6422ea6322b40f4a1c733
출처 데이터셋
uspto-grants-2013_03
특허 번호
US08399493B2

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