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

HRID 447108Notes

Reaction equation

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

Participants

Conditions

Temperature: 50 °C

Procedure

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%).

Workup

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

Sources & evidence

ORD record: ord-7fcfd57bc694488fb59dffc481a67d04
Source dataset: uspto-grants-2013_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08481542B2

Reaction notes

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