1-Bromopropane → 6-Bromo-2-propyl-3,4-dihydroisoquinolin-1(2H)-one

HRID 1891252Notes

Reaction equation

HRID 1891252 reaction equation
[H-].[Na+].[Br:3][C:4]1[CH:5]=[C:6]2[C:11](=[CH:12][CH:13]=1)[C:10](=[O:14])[NH:9][CH2:8][CH2:7]2.Br[CH2:16][CH2:17][CH3:18]>CN(C=O)C>[Br:3][C:4]1[CH:5]=[C:6]2[C:11](=[CH:12][CH:13]=1)[C:10](=[O:14])[N:9]([CH2:16][CH2:17][CH3:18])[CH2:8][CH2:7]2

Participants

5

Reactant 3

HCID 78401-BromopropaneHCID 24758Sodium hydrideHCID 218654506-Bromo-3,4-dihydro-2H-isoquinolin-1-one

Product 1

HCID 671728586-Bromo-2-propyl-3,4-dihydroisoquinolin-1(2H)-oneYield 71.1%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent3×

Procedure

Sodium hydride (60% w/w suspension in oil) (1.17 mmol, 46.7 mg) was suspended in DMF (0.5 ml) under argon. The mixture was cooled to 0° C. before dropwise addition of 6-bromo-3,4-dihydroisoquinolin-1(2H)-one (1K2) (1.06 mmol, 240 mg) in DMF (1.5 ml) The reaction was stirred at 0° C. for 30 min before addition of 3-bromopropane (1K3) (1.592 mmol, 196 mg) in DMF (1 ml). Once addition was complete the reaction was allowed to warm to room temperature then heated at 60° C. for 4hrs. The reaction mixture was cooled, quenched with water and extracted three times with diethyl ether. The combined organics were washed with brine, dried (MgSO4) and evaporated to dryness. The residue was purified on silica eluting with 30-100% EtOAc/heptane to give 6-bromo-2-propyl-3,4-dihydroisoquinolin-1(2H)-one (1K4) 202 mg (70.9%); 1H NMR (400 MHz, CDCl3) δ 7.94 (d, 1H) 7.47 (d, 1H) 7.33 (s, 1H) 3.54 (m, 4H) 2.96 (t, 2H) 1.65 (m, 2H) 0.96 (t, 3H).

Workup

  1. additionOnce addition
  2. temperaturethen heated at 60° C. for 4hrs
  3. temperatureThe reaction mixture was cooled
  4. customquenched with water
  5. extractionextracted three times with diethyl ether
  6. washThe combined organics were washed with brine
  7. dry with materialdried (MgSO4)
  8. customevaporated to dryness
  9. customThe residue was purified on silica eluting with 30-100% EtOAc/heptane

Sources & evidence

ORD record
ord-4127342c4bb34dc7bb29a750d456f04c
Source dataset
uspto-grants-2013_08
Patent number
US08507521B2

Reaction notes

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