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

HRID 1947636Notes

Reaction equation

HRID 1947636 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%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of 5-fluoro-1-indanone (1.5 g, 10 mmol) and methanesulfonic acid (6 ml, 90 mmol) in anhydrous dichloromethane (6 ml) was added sodium azide (1.30 g, 20 mmol) whilst maintaining the temperature of the reaction between 21 and 26° C. The reaction was stirred for 15 hrs and then cooled in ice and basified using 5N sodium hydroxide solution. The organic phase was separated and the aqueous phase extracted with dichloromethane (2×10 ml). The combined organics were washed with water and brine, then dried (MgSO4) and evaporated in vacuo. The resulting residue was purified by flash column chromatography (50% ethyl acetate in dichloromethane) to afford the title compound as a light brown solid (1.0 g, 61%). HPLC retention time 3.18 min. Mass spectrum (ES+) m/z 166 (M+H).

Workup

  1. temperaturewhilst maintaining
  2. customthe temperature of the reaction between 21 and 26° C
  3. temperaturecooled in ice
  4. customThe organic phase was separated
  5. extractionthe aqueous phase extracted with dichloromethane (2×10 ml)
  6. washThe combined organics were washed with water and brine
  7. dry with materialdried (MgSO4)
  8. customevaporated in vacuo
  9. customThe resulting residue was purified by flash column chromatography (50% ethyl acetate in dichloromethane)

Sources & evidence

ORD record
ord-a7713c7132b24b458a8eb568d0c3c1bf
Source dataset
uspto-grants-2013_03
Patent number
US08399481B2

Reaction notes

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