Diethyl Ether → N-(3-{6-methyl-3-[(E)-3-phenyl-2-propenyl]-3-azabicyclo[3.1.0]hex-6-yl}phenyl)methanesulfonamide

HRID 428873Notes

Reaction equation

HRID 428873 reaction equation
[CH3:1][C:2]1([C:8]2[CH:9]=[C:10]([NH:14][S:15]([CH3:18])(=[O:17])=[O:16])[CH:11]=[CH:12][CH:13]=2)[CH:7]2[CH:3]1[CH2:4][NH:5][CH2:6]2.C(=O)([O-])O.[Na+].Br[CH2:25]/[CH:26]=[CH:27]/[C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1.C(OCC)C>O>[NH3:5].[CH3:1][C:2]1([C:8]2[CH:9]=[C:10]([NH:14][S:15]([CH3:18])(=[O:17])=[O:16])[CH:11]=[CH:12][CH:13]=2)[CH:7]2[CH:3]1[CH2:4][N:5]([CH2:25]/[CH:26]=[CH:27]/[C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1)[CH2:6]2

Participants

7

Reactant 4

HCID 3283Diethyl EtherHCID 516892Sodium BicarbonateHCID 5357478Cinnamyl bromideHCID 22141143N-[3-(6-methyl-3-azabicyclo[3.1.0]hex-6-yl)phenyl)methanesulfonamide

Product 2

HCID 222AmmoniaHCID 22141300N-(3-{6-methyl-3-[(E)-3-phenyl-2-propenyl]-3-azabicyclo[3.1.0]hex-6-yl}phenyl)methanesulfonamideYield 23.5%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
50 °C

Procedure

To a solution of the hydrochloride salt of N-[3-(6-methyl-3-azabicyclo[3.1.0]hex-6--yl)phenyl]methanesulfonamide (Preparation 53, 200 mg, 0.89 mmol) in N,N-dimethylfornamide (8 ml) was added sodium hydrogen carbonate (3 g, 36 mmol) and 1-[(E)-3-bromo-1-propenyl]benzene (0.13 ml, 0.89 mmol) and the reaction mixture was heated at 50° C. for 20 h. After cooling, diethyl ether (15 ml) and water (15 ml) were added and the reaction mixture was stirred vigorously for 5 min. The phases were separated and the aqueous layer was further extracted with diethyl ether (2×15 ml). The combined organic extracts were dried (Na2SO4), filtered and concentrated in vacuo. The residual oil was purified by flash column chromatography using a Sep-Pak™ cartridge packed with silica gel (10 g) eluting with dichloromethane:ethanol:0.88 ammonia solution (200:8:1) to afford the title compound as an oil (40 mg, 12%).

Workup

  1. temperatureAfter cooling
  2. customThe phases were separated
  3. extractionthe aqueous layer was further extracted with diethyl ether (2×15 ml)
  4. dry with materialThe combined organic extracts were dried (Na2SO4)
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customThe residual oil was purified by flash column chromatography
  8. washeluting with dichloromethane

Sources & evidence

ORD record
ord-033573be4b8b4eaea47ac07492f38bf2
Source dataset
uspto-grants-2001_11
Patent number
US06313312B1

Reaction notes

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