Methyl iodide → Methyl 4-bromo-5,6,7,8-tetrahydro-7-methyl-8-oxo-7-isoquinolinecarboxylate

HRID 530344Notes

Reaction equation

HRID 530344 reaction equation
[Br:1][C:2]1[C:11]2[CH2:10][CH2:9][CH:8]([C:12]([O:14][CH3:15])=[O:13])[C:7](=[O:16])[C:6]=2[CH:5]=[N:4][CH:3]=1.[H-].[Na+].[CH3:19]I>CN(C=O)C.C1COCC1.O>[CH3:15][O:14][C:12]([C:8]1([CH3:19])[C:7](=[O:16])[C:6]2[CH:5]=[N:4][CH:3]=[C:2]([Br:1])[C:11]=2[CH2:10][CH2:9]1)=[O:13]

Participants

7

Reactant 3

HCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 86679925Methyl 4-bromo-8-oxo-5,6,7,8-tetrahydroisoquinoline-7-carboxylate

Product 1

HCID 89456261Methyl 4-bromo-5,6,7,8-tetrahydro-7-methyl-8-oxo-7-isoquinolinecarboxylateYield 90%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a stirred solution of (rac)-methyl 4-bromo-8-oxo-5,6,7,8-tetrahydroisoquinoline-7-carboxylate (3.5 g, 12.3 mmol) (intermediate A-2 [B]) in DMF (10 mL) and THF (50 mL) was added 60% NaH (750 mg, 18.5 mmol) in portions at 0° C. The reaction mixture was stirred at 0° C. for 15 min before methyl iodide (1.6 mL, 24.6 mmol) was added and the resulting reaction mixture was allowed to warm up to room temperature and stirred over night. The reaction mixture was then diluted with water (10 mL) and extracted with EtOAc (2×100 mL). Combined organics were washed with brine, dried over Na2SO4, filtered and evaporated to dryness. The residue was purified by silica gel flash chromatography eluting with a 0 to 30% EtOAc-heptane gradient to give the title compound (3.3 g, 90% yield) as a light yellow solid. MS: 297.9 & 299.9 (M+H)+.

Workup

  1. additionwas added
  2. customthe resulting reaction mixture
  3. extractionextracted with EtOAc (2×100 mL)
  4. washCombined organics were washed with brine
  5. dry with materialdried over Na2SO4
  6. filtrationfiltered
  7. customevaporated to dryness
  8. customThe residue was purified by silica gel flash chromatography
  9. washeluting with a 0 to 30% EtOAc-heptane gradient

Sources & evidence

ORD record
ord-523c9d78fd534e7e88608d29aab50e28
Source dataset
uspto-grants-2016_05
Patent number
US09353081B2

Reaction notes

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