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

HRID 2361678Notes

Reaction equation

HRID 2361678 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.[N-:12]=[N+]=[N-].[Na+].[OH-].[Na+]>ClCCl.CS(O)(=O)=O>[F:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[C:7](=[O:11])[NH:12][CH2:6][CH2:5]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 58%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 6395Methanesulfonic AcidSolvent

Procedure

To a stirred solution of 5-fluoro-2,3-dihydro-1H-inden-1-one (433 mg, 2.9 mmol) in dichloromethane (2.5 ml) and methanesulfonic acid (2.5 ml) was added sodium azide (378 mg, 5.8 mmol) portionwise at room temperature. Gas evolution was seen immediately and after 3 hours, complete conversion was observed by TLC. The reaction mixture was added dropwise to a rapidly stirred 5M NaOH solution (8 ml) in ice maintaining the internal temperature below 15° C. On complete addition, the aqueous phase (pH 14) was extracted with dichloromethane (3×25 ml). The organics were combined and washed with water (2×25 ml), dried (MgSO4), filtered and concentrated in vacuo. NMR showed a 7:3 mixture of regioisomers that were separated by FCC (using a gradient of eluents 1:1 Hexane/EtOAc to EtOAc) providing the title compound as white solid (267 mg, 58%).

Workup

  1. additionOn complete addition
  2. extractionthe aqueous phase (pH 14) was extracted with dichloromethane (3×25 ml)
  3. washwashed with water (2×25 ml)
  4. dry with materialdried (MgSO4)
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. additiona 7:3 mixture of regioisomers that
  8. customwere separated by FCC (

Sources & evidence

ORD record
ord-0b8d0f567b6e4d00b05ecb2231c7774e
Source dataset
uspto-grants-2014_04
Patent number
US08691804B2

Reaction notes

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