Methylamine → 4-[3-(ethylsulfonyl)propyl]-N-methylbicyclo[2.2.2]octane-1-carboxamide

HRID 22860Notes

Reaction equation

HRID 22860 reaction equation
[CH2:1]([S:3]([CH2:6][CH2:7][CH2:8][C:9]12[CH2:16][CH2:15][C:12]([C:17]([OH:19])=O)([CH2:13][CH2:14]1)[CH2:11][CH2:10]2)(=[O:5])=[O:4])[CH3:2].C(Cl)(=O)C(Cl)=O.[CH3:26][NH2:27]>C(Cl)Cl.CN(C=O)C>[CH2:1]([S:3]([CH2:6][CH2:7][CH2:8][C:9]12[CH2:16][CH2:15][C:12]([C:17]([NH:27][CH3:26])=[O:19])([CH2:13][CH2:14]1)[CH2:11][CH2:10]2)(=[O:5])=[O:4])[CH3:2]

Participants

6

Reactant 3

HCID 6329Methylamine2×HCID 65578Oxalyl chlorideHCID 225916994-[3-(Ethylsulfonyl)propyl]bicyclo[2.2.2]octane-1-carboxylic acid

Product 1

HCID 207550394-[3-(ethylsulfonyl)propyl]-N-methylbicyclo[2.2.2]octane-1-carboxamide

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideCatalystHCID 6344DichloromethaneSolvent

Procedure

Carboxylic acid 11-8 (3.0 g, 11 mmol) was dissolved in 50 mL of anhydrous methylene chloride under nitrogen atmosphere, treated with oxalyl chloride (2 M in methylene chloride, 16.2 mL, 32.4 mmol) and subsequently with 5 drops of DMF. The reaction was stirred at room temperature under nitrogen atmosphere for 90 min, then evaporated and placed under vacuum for 20 min. The acid chloride was dissolved in anhydrous methylene chloride (12 mL), cooled in an ice-bath, and then treated dropwise with a solution of methylamine (2M in THF, 27 mL, 54 mmol). Upon addition of the methylamine, the cooling bath was removed and the reaction stirred at ambient temperature for 30 min. The mixture was diluted with 200 mL of methylene chloride and washed with 1N aqueous HCl, saturated aqueous sodium bicarbonate, and brine. The organic layer was dried over anhydrous sodium sulfate and evaporated. The residue was subjected to chromatography on silica gel eluting with a gradient from 0 to 3% methanol in ethyl acetate to give 4-[3-(ethylsulfonyl)propyl]-N-methylbicyclo[2.2.2]octane-1-carboxamide 11-9 as a white powder. MS (ESI+)=302 (M+1).

Workup

  1. customevaporated
  2. waitplaced under vacuum for 20 min
  3. dissolutionThe acid chloride was dissolved in anhydrous methylene chloride (12 mL)
  4. temperaturecooled in an ice-bath
  5. customthe cooling bath was removed
  6. stirringthe reaction stirred at ambient temperature for 30 min
  7. additionThe mixture was diluted with 200 mL of methylene chloride
  8. washwashed with 1N aqueous HCl, saturated aqueous sodium bicarbonate, and brine
  9. dry with materialThe organic layer was dried over anhydrous sodium sulfate
  10. customevaporated

Sources & evidence

ORD record
ord-d8287baf92924bfb9ae5b00042a0d12a
Source dataset
uspto-grants-2005_02
Patent number
US06849636B2

Reaction notes

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