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

HRID 428870Notes

Reaction equation

HRID 428870 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-])[OH:20].[Na+].[CH:24]1([C:30]2C(CCC=O)=C(S([O-])(=O)=O)C=[CH:34][C:35]=2Br)[CH2:29][CH2:28][CH2:27][CH2:26][CH2:25]1.C(OCC)C>COC(OC)COCC(OC)OC.O>[NH3:5].[CH:24]1([C:30](=[O:20])[CH2:35][CH2:34][N:5]2[CH2:6][CH:7]3[CH:3]([C:2]3([C:8]3[CH:9]=[C:10]([NH:14][S:15]([CH3:18])(=[O:17])=[O:16])[CH:11]=[CH:12][CH:13]=3)[CH3:1])[CH2:4]2)[CH2:29][CH2:28][CH2:27][CH2:26][CH2:25]1

Participants

8

Reactant 4

HCID 3283Diethyl EtherHCID 516892Sodium BicarbonateHCID 22141143N-[3-(6-methyl-3-azabicyclo[3.1.0]hex-6-yl)phenyl)methanesulfonamideHCID 865871903-Cyclohexyl-3-oxopropyl-4-bromobenzenesulfonate

Product 2

HCID 222AmmoniaHCID 9865947N-{3-[3-(3-cyclohexyl-3-oxopropyl)-6-methyl-3-azabicyclo[3.1.0]hex-6-yl]phenyl}methanesulfonamideYield 109.3%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 554377Ethane, 1,1'-oxybis[2,2-dimethoxy-Solvent

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, 57 mg, 0.19 mmol) in dimethoxyethyl ether (2 ml) was added sodium hydrogen carbonate (630 mg, 7.52 mmol), and 3-cyclohexyl-3-oxopropyl-4-bromobenzenesulfonate (Preparation 91, 75 mg, 0.2 mmol) and the reaction mixture was heated at 50° C. for 20 h. After cooling, diethyl ether (5 ml) and water (7 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 (2×5 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 (5 g) eluting with dichloromethane:ethanol:0.88 ammonia solution (200:8:1) to afford the title compound as an oil (42 mg, 52%).

Workup

  1. temperatureAfter cooling
  2. customThe phases were separated
  3. extractionthe aqueous layer was further extracted with diethyl ether (2×5 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-87328c1574e2430f80ef1f208cf5d3d8
Source dataset
uspto-grants-2001_11
Patent number
US06313312B1

Reaction notes

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