Hydrochloric Acid → Methyl 2-(6-bromo-2-(4-fluorophenyl)-1-oxo-1,2-dihydroisoquinolin-3-yl)acetate

HRID 927270Notes

Reaction equation

HRID 927270 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5](B(O)O)=[CH:4][CH:3]=1.[Br:11][C:12]1[CH:13]=[C:14]2[C:19](=[CH:20][CH:21]=1)[C:18](=[O:22])[NH:17][C:16]([CH2:23][C:24]([O:26][CH3:27])=[O:25])=[CH:15]2.N1C=CC=CC=1.Cl>C(Cl)Cl.C([O-])(=O)C.[Cu+2].C([O-])(=O)C>[Br:11][C:12]1[CH:13]=[C:14]2[C:19](=[CH:20][CH:21]=1)[C:18](=[O:22])[N:17]([C:5]1[CH:6]=[CH:7][C:2]([F:1])=[CH:3][CH:4]=1)[C:16]([CH2:23][C:24]([O:26][CH3:27])=[O:25])=[CH:15]2

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 1049PyridineHCID 2856454-Fluorophenylboronic acidHCID 118558141Methyl 2-(6-bromo-1-oxo-1,2-dihydroisoquinolin-3-yl)acetate

Product 1

HCID 118558157Methyl 2-(6-bromo-2-(4-fluorophenyl)-1-oxo-1,2-dihydroisoquinolin-3-yl)acetateYield 25.8%

Reagents, catalysts & solvents 2

HCID 8895Cupric acetateCatalystHCID 6344DichloromethaneSolvent

Procedure

Copper (II) acetate (67.5 mg, 0.371 mmol, 1.10 equiv.) and 4-fluorophenylboronic acid (95 mg, 0.675 mmol, 2.00 equiv.) were added to a stirred mixture of methyl 2-(6-bromo-1-oxo-1,2-dihydroisoquinolin-3-yl)acetate (100 mg, 0.338 mmol) and pyridine (54.6 μl, 0.675 mmol, 2.00 equiv.) in CH2Cl2 (3 mL) and the mixture was stirred in air at room temperature overnight in the presence of 4 Å molecular sieves. 1 N HCl (3 mL) was added to the reaction mixture and extracted with DCM (2×5 mL), dried over Na2SO4, filtered and evaporated to dryness. The residue was purified by column chromatography on silica gel eluting with 0-15-20% EtOAc/hexanes to give 34 mg of methyl 2-(6-bromo-2-(4-fluorophenyl)-1-oxo-1,2-dihydroisoquinolin-3-yl)acetate as a pale yellow solid.

Workup

  1. extractionextracted with DCM (2×5 mL)
  2. dry with materialdried over Na2SO4
  3. filtrationfiltered
  4. customevaporated to dryness
  5. customThe residue was purified by column chromatography on silica gel eluting with 0-15-20% EtOAc/hexanes

Sources & evidence

ORD record
ord-dd88f38c3a3e4a369d294ff4ebf197f3
Source dataset
uspto-grants-2016_03
Patent number
US09290454B2

Reaction notes

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