Pyrrolidine → 1-(3,4-Dichlorobenzyl)-7-methoxy-3,4-dihydronaphthalen-2(1H)-one

HRID 2177063Notes

Reaction equation

HRID 2177063 reaction equation
[CH3:1][O:2][C:3]1[CH:12]=[C:11]2[C:6]([CH2:7][CH2:8][C:9](=[O:13])[CH2:10]2)=[CH:5][CH:4]=1.N1CCCC1.Br[CH2:20][C:21]1[CH:26]=[CH:25][C:24]([Cl:27])=[C:23]([Cl:28])[CH:22]=1.CO.C(Cl)Cl.O>CO.CC#N>[Cl:28][C:23]1[CH:22]=[C:21]([CH:26]=[CH:25][C:24]=1[Cl:27])[CH2:20][CH:10]1[C:11]2[C:6](=[CH:5][CH:4]=[C:3]([O:2][CH3:1])[CH:12]=2)[CH2:7][CH2:8][C:9]1=[O:13]

Participants

7

Reactant 4

HCID 31268PyrrolidineHCID 777857-Methoxy-2-tetraloneHCID 6397264-(Bromomethyl)-1,2-dichlorobenzeneHCID 21958822Dichloromethane methanol water

Product 1

HCID 574671871-(3,4-Dichlorobenzyl)-7-methoxy-3,4-dihydronaphthalen-2(1H)-oneYield 84.4%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6342AcetonitrileSolvent2×

Procedure

15 g (85 mmol) of 7-methoxy-3,4-dihydronaphthalen-2(1H)-one were dissolved in 200 ml of dry MeOH under nitrogen. Then 6.66 g (94 mmol) of pyrrolidine were added dropwise and slowly and the colour changes. The mixture is stirred for one h. The solvent was reduced under vacuo and the residue was dissolved in MeCN. At 5° C. 22.5 g (94 mmol) 4-(bromomethyl)-1,2-dichlorobenzene dissolved in MeCN were added and the mixture was stirred over night at RT. The solvent was reduced under vacuo and the residue was mixed with MeOH/CH2Cl2/H2O 1:1:1 (50 ml, 50 ml, 50 ml) and 10 ml of glacial acid were added. The mixture was stirred over night. Work-up: The reaction mixture was put on ice water and extracted 3× with CH2Cl2. The combined organic layers were washed 1× with NaHCO3 solution and 1× with saturated NaCl solution. The organic phase was dried on MgSO4 and the solvent was evaporated. The residue (31.5 g) was purified by flash-chromatography on silica gel with heptane/EtOAc 2:1. 24.1 g (71.7 mmol, 84%) of the product were obtained.

Workup

  1. customAt 5° C
  2. additionwere added
  3. stirringthe mixture was stirred over night at RT
  4. additionwere added
  5. stirringThe mixture was stirred over night
  6. extractionextracted 3× with CH2Cl2
  7. washThe combined organic layers were washed 1× with NaHCO3 solution and 1× with saturated NaCl solution
  8. customThe organic phase was dried on MgSO4
  9. customthe solvent was evaporated
  10. customThe residue (31.5 g) was purified by flash-chromatography on silica gel with heptane/EtOAc 2:1

Sources & evidence

ORD record
ord-60c6060d00b84fb0bf6e682bc11f1691
Source dataset
uspto-grants-2015_06
Patent number
US09067871B2

Reaction notes

Loading…