Diethyl Ether → N-(3-{3-[2-(1-Adamantyl)ethyl]-6-methyl-3-azabicyclo[3.1.0]hex-6-yl}phenyl)methanesulfonamide

HRID 428871Notes

Reaction equation

HRID 428871 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+].[C:24]12([CH2:34][CH2:35]I)[CH2:33][CH:28]3[CH2:29][CH:30]([CH2:32][CH:26]([CH2:27]3)[CH2:25]1)[CH2:31]2.C(OCC)C>CN(C)C=O.O>[NH3:5].[C:24]12([CH2:34][CH2:35][N:5]3[CH2:6][CH:7]4[CH:3]([C:2]4([C:8]4[CH:9]=[C:10]([NH:14][S:15]([CH3:18])(=[O:17])=[O:16])[CH:11]=[CH:12][CH:13]=4)[CH3:1])[CH2:4]3)[CH2:25][CH:26]3[CH2:32][CH:30]([CH2:29][CH:28]([CH2:27]3)[CH2:33]1)[CH2:31]2

Participants

8

Reactant 4

HCID 3283Diethyl EtherHCID 516892Sodium BicarbonateHCID 22141143N-[3-(6-methyl-3-azabicyclo[3.1.0]hex-6-yl)phenyl)methanesulfonamideHCID 221412941-(2-Iodoethyl)adamantane

Product 2

HCID 222AmmoniaHCID 22141358N-(3-{3-[2-(1-Adamantyl)ethyl]-6-methyl-3-azabicyclo[3.1.0]hex-6-yl}phenyl)methanesulfonamideYield 78.6%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

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 N,N-dimethylformamide (2 ml) was added sodium hydrogen carbonate (630 mg, 7.52 mmol) and 1-adamantyl-2-iodoethane (Preparation 93, 58 mg, 0.2 mmol) and the reaction 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 (32 mg, 39%).

Workup

  1. additionwere added
  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-997d0673c36f4c26807d8d9ae65764b4
Source dataset
uspto-grants-2001_11
Patent number
US06313312B1

Reaction notes

Loading…