Cesium fluoride → 5-Bromo-2-(2,2-difluoropropyl)-1,2,3,4-tetrahydroisoquinoline

HRID 1505044Notes

Reaction equation

HRID 1505044 reaction equation
[Br:1][C:2]1[CH:11]=[CH:10][CH:9]=[C:8]2[C:3]=1[CH2:4][CH2:5][N:6]([CH2:12][C:13](=O)[CH3:14])[CH2:7]2.C(N(S(F)(F)[F:22])CC)C.[F-:25].[Cs+].C([O-])(O)=O.[Na+]>C(Cl)Cl.C(O)(C(F)(F)F)=O>[Br:1][C:2]1[CH:11]=[CH:10][CH:9]=[C:8]2[C:3]=1[CH2:4][CH2:5][N:6]([CH2:12][C:13]([F:22])([F:25])[CH3:14])[CH2:7]2

Participants

7

Reactant 4

HCID 25953Cesium fluorideHCID 123472(Diethylamino)sulfur trifluorideHCID 516892Sodium BicarbonateHCID 583180431-(5-Bromo-3,4-dihydroisoquinolin-2(1H)-yl)propan-2-one

Product 1

HCID 583179355-Bromo-2-(2,2-difluoropropyl)-1,2,3,4-tetrahydroisoquinoline

Reagents, catalysts & solvents 2

HCID 6422Trifluoroacetic acidCatalystHCID 6344DichloromethaneSolvent

Procedure

To a solution of 1-(5-bromo-3,4-dihydroisoquinolin-2(1H)-yl)propan-2-one (962 mg, 3.59 mmol), diethylamino sulfur trifluoride (1.74 g, 10.8 ml) in DCM (12 ml) is added cesium fluoride (151 mg, 1 mmol) in small portions, then a few drops of TFA at room temperature. The mixture is stirred for 18 hours at room temperature. To this solution is added saturated aqueous NaHCO3 to quench the reaction. The aqueous layer is extracted with DCM (50 ml×3). The combined organic layers are washed with water, brine, dried over MgSO4 and concentrated. The residue is purified by silica gel flash chromatography, eluted with 20% ethyl acetate in hexanes to yield 5-Bromo-2-(2,2-difluoropropyl)-1,2,3,4-tetrahydroisoquinoline as a brown oil. LC-MS m/z: 291.1 (M+1).

Workup

  1. customat room temperature
  2. customto quench
  3. customthe reaction
  4. extractionThe aqueous layer is extracted with DCM (50 ml×3)
  5. washThe combined organic layers are washed with water, brine
  6. dry with materialdried over MgSO4
  7. concentrationconcentrated
  8. customThe residue is purified by silica gel flash chromatography
  9. washeluted with 20% ethyl acetate in hexanes

Sources & evidence

ORD record
ord-47a4b8a206f54694879b129ae950a696
Source dataset
uspto-grants-2015_12
Patent number
US09216964B2

Reaction notes

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