3-Phenylpropylamine → 6-Methyl-6-(3-nitrophenyl)-3-(3-phenylpropyl)-3-azabicyclo[3.1.0]hexan-2-one

HRID 428903Notes

Reaction equation

HRID 428903 reaction equation
Cl[CH2:2][CH:3]1[CH:5]([C:6]([O:8]CC)=O)[C:4]1([CH3:20])[C:11]1[CH:16]=[CH:15][CH:14]=[C:13]([N+:17]([O-:19])=[O:18])[CH:12]=1.C(=O)([O-])O.[Na+].[C:26]1([CH2:32][CH2:33][CH2:34][NH2:35])[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1>CN(C)C=O>[CH3:20][C:4]1([C:11]2[CH:16]=[CH:15][CH:14]=[C:13]([N+:17]([O-:19])=[O:18])[CH:12]=2)[CH:5]2[CH:3]1[CH2:2][N:35]([CH2:34][CH2:33][CH2:32][C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1)[C:6]2=[O:8]

Participants

5

Reactant 3

HCID 162593-PhenylpropylamineHCID 516892Sodium BicarbonateHCID 22141336Ethyl 3-(chloromethyl)-2-methyl-2-(3-nitrophenyl)cyclopropanecarboxylate

Product 1

HCID 221412666-Methyl-6-(3-nitrophenyl)-3-(3-phenylpropyl)-3-azabicyclo[3.1.0]hexan-2-one

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
150 °C

Procedure

To a solution of ethyl 3-(chloromethyl)-2-methyl-2-(3-nitrophenyl)-cyclopropane carboxylate (Preparation 5, 14.4 g, 48.6 mmol), in N,N-dimethylformamide (120 Ml) was added sodium hydrogen carbonate (12 g, 143 mmol) and 3-phenylpropylamine (38.8 g, 41 ml, 290 mmol). The mixture was heated to 150° C. for 7 h, then cooled to room temperature and poured onto water (1000 ml). The mixture was extracted with diethyl ether (2×500 ml), and the combined extracts were washed with water (2×250 ml), dried (Na2SO4), filtered and concentrated in vacuo. The residue was purified by silica (1000 g) column chromatography eluting with dichloromethane then dichloromethane/ethyl acetate 4:1. Product-containing fractions were combined and concentrated in vacuo to give the title compound as a very pale yellow oil (6.2 g, 36%).

Workup

  1. temperaturecooled to room temperature
  2. additionpoured onto water (1000 ml)
  3. extractionThe mixture was extracted with diethyl ether (2×500 ml)
  4. washthe combined extracts were washed with water (2×250 ml)
  5. dry with materialdried (Na2SO4)
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customThe residue was purified by silica (1000 g) column chromatography
  9. washeluting with dichloromethane
  10. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-135330bf5bb144f9824405326797212b
Source dataset
uspto-grants-2001_11
Patent number
US06313312B1

Reaction notes

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