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

HRID 428874Notes

Reaction equation

HRID 428874 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.Cl.C(=O)([O-])O.[Na+].BrC1C=CC(S(O[CH2:36][CH2:37][C@@H:38]([CH:40]2[CH2:45][CH2:44][CH2:43][CH2:42][CH2:41]2)[OH:39])(=O)=O)=CC=1.C(OCC)C>CN(C)C=O.O>[NH3:5].[CH:40]1([CH:38]([OH:39])[CH2:37][CH2:36][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)[CH2:45][CH2:44][CH2:43][CH2:42][CH2:41]1

Participants

8

Reactant 4

HCID 3283Diethyl EtherHCID 516892Sodium BicarbonateHCID 10643291(S)-3-cyclohexyl-3-hydroxypropyl 4-bromobenzenesulfonateHCID 22141325N-[3-(6-methyl-3-azabicyclo[3.1.0]hex-6-yl)phenyl]methanesulfonamide hydrochloride salt

Product 2

HCID 222AmmoniaHCID 9909306N-{3-[3-(3-Cyclohexyl-3-hydroxypropyl)-6-methyl-3-azabicyclo[3.1.0]hex-6-yl]phenyl}methanesulfonamideYield 25%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
50 °C

Procedure

To a solution of hydrochloride salt N-[3-(6-methyl-3-azabicyclo[3.1.0]hex-6-yl)phenyl]methanesulfonamide (Preparation 53, 200 mg, 0.66 mmol) in N,N-dimethylformamide (8 ml) was added sodium hydrogen carbonate (3 g, 36 mmol) and (S)-3-cyclohexyl-3-hydroxypropyl 4-bromobenzenesulfonate (J. A. Werner et al, J. Org. Chem., 1996, 61, 587) (0.08 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 (90 mg, 25%).

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-a7f91e75648b413bac35083688aa2f7c
Source dataset
uspto-grants-2001_11
Patent number
US06313312B1

Reaction notes

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