Methanesulfonic Acid → 6-Fluoro-1,2,3,4-tetrahydroisoquinolin-1-one

HRID 2245714Notes

Reaction equation

HRID 2245714 reaction equation
[F:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[C:7](=[O:11])[CH2:6][CH2:5]2.CS(O)(=O)=O.[N-:17]=[N+]=[N-].[Na+].[OH-].[Na+]>ClCCl>[F:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[C:7](=[O:11])[NH:17][CH2:6][CH2:5]2

Participants

6

Reactant 4

HCID 6395Methanesulfonic AcidHCID 14798Sodium HydroxideHCID 33557Sodium AzideHCID 1365375-Fluoro-1-indanone

Product 1

HCID 107257096-Fluoro-1,2,3,4-tetrahydroisoquinolin-1-oneYield 61.1%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

To 25.0 g (166.15 mmol) 5-fluoroindanone in a 3 L flask equipped with a mechanical stirrer was added 280 ml dichloromethane and 200 ml methanesulfonic acid. The mixture was cooled to 0° C. and 15.15 g (233.1 mmol) sodium azide was added in portions over 20 minutes. The mixture was stirred at 0° C. for 2 h, then 490 ml 20% aqueous sodium hydroxide was added dropwise over 30 minutes. The layers were separated and the organic phase dried over MgSO4 and concentrated. Purification by column chromatography eluting with ethyl acetate/hexanes provided 16.76 g (61%) of the desired 6-fluoro-3,4-dihydroisoquinolinone isomer.

Workup

  1. customThe layers were separated
  2. dry with materialthe organic phase dried over MgSO4
  3. concentrationconcentrated
  4. customPurification by column chromatography
  5. washeluting with ethyl acetate/hexanes

Sources & evidence

ORD record
ord-953bed96ba7d45cb9d80ad48549e6afb
Source dataset
uspto-grants-2010_03
Patent number
US07683064B2

Reaction notes

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