Methanol → 1-(1-(3,4-Dichlorobenzyl)-7-methoxy-1,2,3,4-tetrahydronaphthalen-2-yl)pyrrolidine

HRID 510522Notes

Reaction equation

HRID 510522 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([CH:19]=[CH:20][C:21]=1[Cl:22])[CH2:5][CH:6]1[C:15]2[C:10](=[CH:11][CH:12]=[C:13]([O:16][CH3:17])[CH:14]=2)[CH2:9][CH2:8][C:7]1=O.[NH:23]1[CH2:27][CH2:26][CH2:25][CH2:24]1.CO.C#N.[Na]>C1(C)C=CC=CC=1.O.C1(C)C=CC(S(O)(=O)=O)=CC=1.O>[Cl:1][C:2]1[CH:3]=[C:4]([CH:19]=[CH:20][C:21]=1[Cl:22])[CH2:5][CH:6]1[C:15]2[C:10](=[CH:11][CH:12]=[C:13]([O:16][CH3:17])[CH:14]=2)[CH2:9][CH2:8][CH:7]1[N:23]1[CH2:27][CH2:26][CH2:25][CH2:24]1

Participants

8

Reactant 4

HCID 887MethanolHCID 31268PyrrolidineHCID 44134943Sodium cyanohydrideHCID 574671871-(3,4-Dichlorobenzyl)-7-methoxy-3,4-dihydronaphthalen-2(1H)-one

Product 1

HCID 574712301-(1-(3,4-Dichlorobenzyl)-7-methoxy-1,2,3,4-tetrahydronaphthalen-2-yl)pyrrolidineYield 25%

Reagents, catalysts & solvents 3

HCID 521998p-Toluenesulfonic acid monohydrateCatalystHCID 962WaterSolventHCID 1140TolueneSolvent

Procedure

1-(3,4-Dichlorobenzyl)-7-methoxy-3,4-dihydronaphthalen-2(1H)-one (5.5 g, 16.4 mmol, example 1), pyrrolidine (1.40 g, 19.7 mmol), and p-toluenesulfonic acid monohydrate (31.0 mg, 0.164 mmol) were dissolved in toluene (100 ml) and refluxed for 2 h using a Dean-Stark condenser. The solvent was removed and after addition of MeOH (50 ml) and sodium cyanohydride (1.57 g, 24.6 mmol) the mixture was stirred for 4 d at room temperature under nitrogen. Water was added, the organic phase separated and the aqueous phase extracted with ethyl acetate. The combined organic layers were washed with saturated NaCl solution, dried over MgSO4, and concentrated to afford a residue that was purified by flash chromatography (silica gel, MeOH/CH2Cl23:97→5:95). The beige solid product (1.6 g, 25%) was obtained from precipitation in ethyl acetate/diisopropylether (1:1).

Workup

  1. temperaturerefluxed for 2 h
  2. customThe solvent was removed
  3. customthe organic phase separated
  4. extractionthe aqueous phase extracted with ethyl acetate
  5. washThe combined organic layers were washed with saturated NaCl solution
  6. dry with materialdried over MgSO4
  7. concentrationconcentrated
  8. customto afford a residue that
  9. customwas purified by flash chromatography (silica gel, MeOH/CH2Cl23:97→5:95)

Sources & evidence

ORD record
ord-661773667f244dd1a7434b45065ba32b
Source dataset
uspto-grants-2015_08
Patent number
US09096619B2

Reaction notes

Loading…