1,4-Dichloro-5,6,7,8-tetrahydrophthalazine → 1-Chloro-4-(4-fluorobenzyl)-5,6,7,8-tetrahydrophthalazine

HRID 447108노트

반응식

HRID 447108 반응식
Cl[C:2]1[C:11]2[CH2:10][CH2:9][CH2:8][CH2:7][C:6]=2[C:5]([Cl:12])=[N:4][N:3]=1.[Cl-].[F:14][C:15]1[CH:22]=[CH:21][C:18]([CH2:19][Zn+])=[CH:17][CH:16]=1>C1COCC1>[Cl:12][C:5]1[C:6]2[CH2:7][CH2:8][CH2:9][CH2:10][C:11]=2[C:2]([CH2:19][C:18]2[CH:21]=[CH:22][C:15]([F:14])=[CH:16][CH:17]=2)=[N:3][N:4]=1

참가 물질

4

반응물 2

HCID 126224401,4-Dichloro-5,6,7,8-tetrahydrophthalazine2회HCID 178505764HCID 178505764, 화합물

생성물 1

HCID 574716251-Chloro-4-(4-fluorobenzyl)-5,6,7,8-tetrahydrophthalazine수율 74.9%

시약·촉매·용매 1

HCID 8028Tetrahydrofuran용매

반응 조건

온도
50 °C

실험 절차

To a solution of 1,4-dichloro-5,6,7,8-tetrahydro-phthalazine (compound 41, 0.50 g, 2.46 mmol) in THF (5 mL) are added 4-fluoro-benzyl zincchloride (0.5M in THF) (6.40 mL, 3.20 mmol) and palladium tetrakis triphenylphosphine (0.36 g, 0.31 mmol). The mixture is degassed and stirred at 50° C. overnight. Then the reaction mixture is cooled down to room temperature, sat. NaHCO3 and water are added and the mixture is extracted with EtOAc. The combined organic layers are washed with brine, dried over Na2SO4, filtered and concentrated down. The crude product is purified by chromatography (EtOAc/heptane: 10%˜40%) to give 1-chloro-4-(4-fluoro-benzyl)-5,6,7,8-tetrahydro-phthalazine (46) (0.51 g, 30%).

후처리

  1. customThe mixture is degassed
  2. temperatureThen the reaction mixture is cooled down to room temperature
  3. additionsat. NaHCO3 and water are added
  4. extractionthe mixture is extracted with EtOAc
  5. washThe combined organic layers are washed with brine
  6. dry with materialdried over Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated down
  9. customThe crude product is purified by chromatography (EtOAc/heptane: 10%˜40%)

출처 및 근거

ORD 기록
ord-7fcfd57bc694488fb59dffc481a67d04
출처 데이터셋
uspto-grants-2013_07
특허 번호
US08481542B2

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