Diethylamine → HCID 68828193, compound

HRID 2099347Notes

Reaction equation

HRID 2099347 reaction equation
O=C(Cl)[O:3][C:4](Cl)(Cl)Cl.[CH:9]1([NH:15][CH:16]2[CH2:22][CH:21]3[N:23]([C:24]([O:26][C:27]([CH3:30])([CH3:29])[CH3:28])=[O:25])[CH:18]([CH2:19][CH2:20]3)[CH2:17]2)[CH2:14][CH2:13][CH2:12][CH2:11][CH2:10]1.[CH2:31]([N:33](CC)[CH2:34][CH3:35])[CH3:32].C(NCC)C>ClCCl>[CH:9]1([N:15]([C:4]([N:33]([CH2:34][CH3:35])[CH2:31][CH3:32])=[O:3])[CH:16]2[CH2:17][CH:18]3[N:23]([C:24]([O:26][C:27]([CH3:30])([CH3:29])[CH3:28])=[O:25])[CH:21]([CH2:20][CH2:19]3)[CH2:22]2)[CH2:10][CH2:11][CH2:12][CH2:13][CH2:14]1

Participants

6

Reactant 4

HCID 8021DiethylamineHCID 8471Triethylamine2×HCID 10426Diphosgene2×HCID 68829044HCID 68829044, compound

Product 1

HCID 68828193HCID 68828193, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Conditions

Temperature
0 °C

Procedure

0.64 ml of diphosgene is placed in 10 ml of dichloromethane at 0° C. under N2. A solution of 1.0 g of tert-butyl 3-(cyclohexylamino)-8-azabicyclo[3.2.1]-octane-8-carboxylate endo compound and 2.26 ml of triethylamine in 10 ml of dichloromethane is added dropwise. The solution is stirred at 0° C. for 30 min and then at ambient temperature for 4 h. 5 ml of triethylamine and 1.0 ml of diphosgene are then added. After stirring at ambient temperature for 2 h, 1.68 ml of diethylamine are added. The mixture is stirred at ambient temperature for 16 h. After concentration, 0.5N hydrochloric acid is added up to an acid pH. Extraction is carried out with dichloromethane until the aqueous phase is completely depleted. The organic phase is washed with H2O, and then with a saturated aqueous sodium chloride solution. After drying over MgSO4 and concentration to dryness, the residue obtained is chromatographed on silica gel, elution being carried out with a 99/1 and then 95/5 mixture of dichloromethane and methanol, to give 1.60 g of tert-butyl 3-{cyclohexyl[(diethylamino)carbonyl]amino}-8-azabicyclo[3.2.1]octane-8-carboxylate as a mixture with diethylurea.

Workup

  1. additionis added dropwise
  2. waitat ambient temperature for 4 h
  3. stirringAfter stirring at ambient temperature for 2 h
  4. stirringThe mixture is stirred at ambient temperature for 16 h
  5. concentrationAfter concentration, 0.5N hydrochloric acid
  6. additionis added up to an acid pH
  7. extractionExtraction
  8. washThe organic phase is washed with H2O
  9. dry with materialAfter drying over MgSO4 and concentration to dryness
  10. customthe residue obtained
  11. customis chromatographed on silica gel, elution
  12. addition95/5 mixture of dichloromethane and methanol

Sources & evidence

ORD record
ord-765dac1cea6349ff9b799222c1b31a10
Source dataset
uspto-grants-2009_08
Patent number
US07569582B2

Reaction notes

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