Methanesulfonic Acid → 6-Bromo-3,4-dihydro-2H-isoquinolin-1-one

HRID 1891251Notes

Reaction equation

HRID 1891251 reaction equation
[Br: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+]>C(Cl)Cl>[Br: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

5

Reactant 3

HCID 6395Methanesulfonic AcidHCID 33557Sodium AzideHCID 5206955-Bromo-1-indanone

Product 1

HCID 218654506-Bromo-3,4-dihydro-2H-isoquinolin-1-oneYield 42.9%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

5-bromo-2,3-dihydro-1H-inden-1-one (1K1) (9.48 mmol, 2 g) was dissolved in DCM (35 ml) and methane sulfonic acid (95 mmol, 9.11 g) was added. The reaction mixture was cooled to 0° C. before portionwise addition of sodium azide (28.4 mmol, 1.85 g). Once addition was complete the mixture was allowed to warm to room temperature and stirred overnight. The reaction mixture was partitioned between DCM and NaOH (2M, 50 ml). The phases were separated and the aqueous layer was extracted twice more with DCM. The combined organics were washed with water and brine, dried (MgSO4) and evaporated to dryness before purification on silica eluting with 75-100% EtOAc/heptane to give 6-bromo-3,4-dihydroisoquinolin-1(2H)-one (1K2) 919 mg (42%) 1H NMR (400 MHz, CDCl3) δ 7.93 (d, 1H) 7.49 (d, 1H) 7.40 (s, 1H) 6.36 (bs, 1H) 3.58 (t, 2H) 2.99 (t, 2H).

Workup

  1. additionOnce addition
  2. customThe reaction mixture was partitioned between DCM and NaOH (2M, 50 ml)
  3. customThe phases were separated
  4. extractionthe aqueous layer was extracted twice more with DCM
  5. washThe combined organics were washed with water and brine
  6. dry with materialdried (MgSO4)
  7. customevaporated to dryness before purification on silica eluting with 75-100% EtOAc/heptane

Sources & evidence

ORD record
ord-d24d34d91b6c4243b84e5a4382cab204
Source dataset
uspto-grants-2013_08
Patent number
US08507521B2

Reaction notes

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