Sodium Hydroxide → 6-Fluoro-1,2,3,4-tetrahydroisoquinolin-1-one

HRID 2303321Notes

Reaction equation

HRID 2303321 reaction equation
[N-:1]=[N+]=[N-].[Na+].[F:5][C:6]1[CH:7]=[C:8]2[C:12](=[CH:13][CH:14]=1)[C:11](=[O:15])[CH2:10][CH2:9]2.[OH-].[Na+]>CS(O)(=O)=O.ClCCl>[F:5][C:6]1[CH:7]=[C:8]2[C:12](=[CH:13][CH:14]=1)[C:11](=[O:15])[NH:1][CH2:10][CH2:9]2

Participants

6

Reactant 3

HCID 14798Sodium HydroxideHCID 33557Sodium AzideHCID 1365375-Fluoro-1-indanone

Product 1

HCID 107257096-Fluoro-1,2,3,4-tetrahydroisoquinolin-1-oneYield 78.7%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 6395Methanesulfonic AcidSolvent

Procedure

Sodium azide (7.8 g, 120 mmol) was added portionwise to a stirred solution of 5-fluoro indanone (9 g, 60 mmol) in methanesulfonic acid (35 mL) and dichloromethane (35 mL), while the temperature was maintained between 22°-29° C. Once addition was completed, the mixture was stirred at room temperature for 16 hours. The mixture was cooled to 0° C. and neutralized by the addition of 5N-NaOH solution and the organic layer separated. The aqueous layer was washed with dichloromethane (3×50 mL) and the combined organics washed with water (50 mL), brine (50 mL) and dried over anhydrous sodium sulfate. Filtration and concentration gave a light oil (7.8 g) which was purified by flash silica gel chromatography (eluted with diethyl ether) to afford the titled compound as a white solid.

Workup

  1. temperaturewas maintained between 22°-29° C
  2. additionOnce addition
  3. temperatureThe mixture was cooled to 0° C.
  4. customthe organic layer separated
  5. washThe aqueous layer was washed with dichloromethane (3×50 mL)
  6. washthe combined organics washed with water (50 mL), brine (50 mL)
  7. dry with materialdried over anhydrous sodium sulfate
  8. filtrationFiltration and concentration

Sources & evidence

ORD record
ord-549ab1e4e2144eeda5335e5d59fb6200
Source dataset
uspto-grants-2002_08
Patent number
US06432974B1

Reaction notes

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