Sodium hydride → HCID 19010524, compound

HRID 1741731Notes

Reaction equation

HRID 1741731 reaction equation
[H-].[Na+].[Br:3][C:4]1[CH:5]=[C:6]2[C:11](=[CH:12][CH:13]=1)[C:10](=[O:14])[NH:9][CH2:8][CH2:7]2.[F:15][C:16]1[CH:21]=[CH:20][C:19]([C:22]2[CH:23]=[CH:24][C:25]([CH2:28]Cl)=[N:26][CH:27]=2)=[CH:18][CH:17]=1>CN(C=O)C>[Br:3][C:4]1[CH:5]=[C:6]2[C:11](=[CH:12][CH:13]=1)[C:10](=[O:14])[N:9]([CH2:28][C:25]1[CH:24]=[CH:23][C:22]([C:19]3[CH:20]=[CH:21][C:16]([F:15])=[CH:17][CH:18]=3)=[CH:27][N:26]=1)[CH2:8][CH2:7]2

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 19010529HCID 19010529, compoundHCID 218654506-Bromo-3,4-dihydro-2H-isoquinolin-1-one

Product 1

HCID 19010524HCID 19010524, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent3×

Procedure

To a cooled (0° C.) suspension of NaH (0.084 g. 3.5 mmol) and Kl (0.1 g, 0.6 mmol) in DMF (10 mL) is added dropwise a solution of 6-bromo-1-oxo-1,2,3,4-tetrahydroisoquinoline (0.65 g, 2.9 mmol) in DMF (10 mL). After 15 minutes, a solution of 5-(4-fluorophenyl)-2-(chloromethyl)pyridine (1.27 g, 5.8 mmol) in DMF (10 mL) is added dropwise and the resulting solution stirred for 12 hours. The reaction mixture is then partitioned between water (200 mL) and EtOAc (200 mL). The aqueous layer is extracted with EtOAc (1×200 mL). The combined organic extracts are then washed with H2O (4×200 mL), saturated NaCl solution (2×200 mL), and dried over MgSO4 and concentrated in vacuo. The resulting material is chromatographed (silica gel. 1:4 EtOAc-hexanes) to afford 6-bromo-2-{[5-(4-fluorophenyl)-2-pyridyl]methyl}-1-oxo-1,2,3,4 -tetrahydroisoquinoline as pale yellow oil.

Workup

  1. temperatureTo a cooled
  2. customThe reaction mixture is then partitioned between water (200 mL) and EtOAc (200 mL)
  3. extractionThe aqueous layer is extracted with EtOAc (1×200 mL)
  4. washThe combined organic extracts are then washed with H2O (4×200 mL), saturated NaCl solution (2×200 mL)
  5. dry with materialdried over MgSO4
  6. concentrationconcentrated in vacuo
  7. customThe resulting material is chromatographed (silica gel. 1:4 EtOAc-hexanes)

Sources & evidence

ORD record
ord-ae60e1995316417aa18d1d1c893c9d46
Source dataset
uspto-grants-1994_08
Patent number
US05334600

Reaction notes

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