Triethylamine → N-[8-Methyl-8-azabicyclo[3.2.1]oct-3-yl]-[7-(tert-butoxy-carbonyl)-7-azaspiro[3.5]non-2-yl]acetamide

HRID 1059357Notes

Reaction equation

HRID 1059357 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:20][CH2:19][C:11]2([CH2:14][CH:13]([CH2:15][C:16](O)=[O:17])[CH2:12]2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].C(N(CC)CC)C.ClC(OCC)=O.Cl.Cl.[NH2:36][CH:37]1[CH2:43][CH:42]2[N:44]([CH3:45])[CH:39]([CH2:40][CH2:41]2)[CH2:38]1>ClCCl.O>[CH3:45][N:44]1[CH:39]2[CH2:40][CH2:41][CH:42]1[CH2:43][CH:37]([NH:36][C:16](=[O:17])[CH2:15][CH:13]1[CH2:12][C:11]3([CH2:10][CH2:9][N:8]([C:6]([O:5][C:1]([CH3:2])([CH3:3])[CH3:4])=[O:7])[CH2:20][CH2:19]3)[CH2:14]1)[CH2:38]2

Participants

7

Reactant 4

HCID 8471Triethylamine2×HCID 10928Ethyl chloroformateHCID 27759288-methyl-8-azabicyclo[3.2.1]octan-3-amine DihydrochlorideHCID 186705702-(7-((Tert-butoxy)carbonyl)-7-azaspiro(3.5)nonan-2-yl)acetic acid

Product 1

HCID 18670154N-[8-Methyl-8-azabicyclo[3.2.1]oct-3-yl]-[7-(tert-butoxy-carbonyl)-7-azaspiro[3.5]non-2-yl]acetamideYield 51.4%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent

Procedure

1.7 g of [7-(tert-butoxycarbonyl)-7-azaspiro[3.5]non-2-yl]acetic acid was dissolved in 50 ml of dichloromethane. After adding 0.9 ml of triethylamine, the resulting mixture was ice-cooled. After adding 0.95 ml of ethyl chloroformate, the resulting mixture was stirred at room temperature for 30 minutes. Then 1.9 g of 3-amino-8-methyl-8-azabicyclo[3.2.1]octane dihydrochloride and 2.5 ml of triethylamine were added thereto and the resulting mixture was stirred at room temperature for 6 hours. After adding water, the reaction mixture was extracted with ethyl acetate. The organic layer was washed with 1 N sodium hydroxide and dried over anhydrous magnesium sulfate. After distilling off the solvent under reduced pressure, the obtained crystals were washed with ether to thereby give 1.25 g of the title compound as white crystals.

Workup

  1. temperaturecooled
  2. stirringthe resulting mixture was stirred at room temperature for 6 hours
  3. extractionthe reaction mixture was extracted with ethyl acetate
  4. washThe organic layer was washed with 1 N sodium hydroxide
  5. dry with materialdried over anhydrous magnesium sulfate
  6. distillationAfter distilling off the solvent under reduced pressure
  7. washthe obtained crystals were washed with ether

Sources & evidence

ORD record
ord-8dfb3b473795422fb268f356f353d9b7
Source dataset
uspto-grants-2003_02
Patent number
US06518423B1

Reaction notes

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