Dimethylformamide → N-2-adamantyl-4-[3-(ethylsulfonyl)propyl]bicyclo[2.2.2]octane-1-carboxamide

HRID 605516Notes

Reaction equation

HRID 605516 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.CN(C=O)C.[CH:31]12[CH2:40][CH:35]3[CH2:36][CH:37]([CH2:39][CH:33]([CH2:34]3)[CH:32]1[NH2:41])[CH2:38]2>C(Cl)Cl.C(N(CC)CC)C>[CH:31]12[CH2:40][CH:35]3[CH2:36][CH:37]([CH2:39][CH:33]([CH2:34]3)[CH:32]1[NH:41][C:17]([C:12]13[CH2:11][CH2:10][C:9]([CH2:8][CH2:7][CH2:6][S:3]([CH2:1][CH3:2])(=[O:4])=[O:5])([CH2:14][CH2:13]1)[CH2:16][CH2:15]3)=[O:19])[CH2:38]2

Participants

7

Reactant 4

HCID 6228DimethylformamideHCID 253322-AminoadamantaneHCID 65578Oxalyl chlorideHCID 225916994-[3-(Ethylsulfonyl)propyl]bicyclo[2.2.2]octane-1-carboxylic acid

Product 1

HCID 11604197N-2-adamantyl-4-[3-(ethylsulfonyl)propyl]bicyclo[2.2.2]octane-1-carboxamide

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolvent2×HCID 8471TriethylamineSolvent

Procedure

Carboxylic acid 2-8 (0.100 g, 0.348 mmol) was dissolved in 2 mL of anhydrous methylene chloride under nitrogen atmosphere, treated with oxalyl chloride (2 M in methylene chloride, 2 eq., 0.348 mL, 0.696 mmol) and subsequently with 0.050 ml 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 (2 mL), and then treated with triethylamine (0.100 ml) and 2-adamantylamine (2 eq., 105 mg). The reaction stirred at ambient temperature for 1 hr. The mixture was diluted with 20 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 product was purified using a Gilson HPLC with UV detection equipped with a C18 reverse phase column running a gradient of water/acetonitrile (0.1% TFA). The fractions containing product were concentrated to remove some of the acetonitrile and the lyophilized to provide pure product N-2-adamantyl-4-[3-(ethylsulfonyl)propyl]bicyclo[2.2.2]octane-1-carboxamide (2-9) as a white fluffy amorphous solid.

Workup

  1. customevaporated
  2. waitplaced under vacuum for 20 min
  3. dissolutionThe acid chloride was dissolved in anhydrous methylene chloride (2 mL)
  4. stirringThe reaction stirred at ambient temperature for 1 hr
  5. washwashed with 1N aqueous HCl, saturated aqueous sodium bicarbonate, and brine
  6. dry with materialThe organic layer was dried over anhydrous sodium sulfate
  7. customevaporated
  8. customThe product was purified
  9. customequipped with a C18 reverse phase column
  10. additionThe fractions containing product
  11. concentrationwere concentrated
  12. customto remove some of the acetonitrile

Sources & evidence

ORD record
ord-087d336b96fd459f94db83efe11579d0
Source dataset
uspto-grants-2011_03
Patent number
US07915252B2

Reaction notes

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