Ammonia → HCID 9933901, compound

HRID 1359374Notes

Reaction equation

HRID 1359374 reaction equation
CN(C)C=O.FC(F)(F)S(O[C:12]1[C:13]([CH2:28][C:29]2[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=2)=[N:14][C:15]([N:18]2[CH2:22][CH2:21][C:20]3([O:26][CH2:25][CH2:24][O:23]3)[C:19]2=[O:27])=[CH:16][CH:17]=1)(=O)=O.[C:37]([C@:39]1([OH:47])[CH:44]2[CH2:45][CH2:46][N:41]([CH2:42][CH2:43]2)[CH2:40]1)#[CH:38].N>C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C(OCC)(=O)C.C(N(CC)CC)C>[CH2:28]([C:13]1[C:12]([C:38]#[C:37][C@:39]2([OH:47])[CH:44]3[CH2:45][CH2:46][N:41]([CH2:42][CH2:43]3)[CH2:40]2)=[CH:17][CH:16]=[C:15]([N:18]2[CH2:22][CH2:21][C:20]3([O:23][CH2:24][CH2:25][O:26]3)[C:19]2=[O:27])[N:14]=1)[C:29]1[CH:30]=[CH:31][CH:32]=[CH:33][CH:34]=1

Participants

8

Reactant 4

HCID 222AmmoniaHCID 6228DimethylformamideHCID 946095(3R)-3-ethynyl-1-azabicyclo[2.2.2]octan-3-olHCID 18182279HCID 18182279, compound

Product 1

HCID 9933901HCID 9933901, compoundYield 60.7%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 8471TriethylamineSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
60 °C

Procedure

7 ml of N,N-dimethylformamide was added to a mixture of 1.1 g of 2-benzyl-6-(3,3-ethylenedioxy-2-pyrrolidinone-1-yl)-3-pyridyl trifluoromethanesulfonate, 437 mg of (3R)-3-ethynyl-3-quinuclidinol, 168 mg of tetrakis(triphenylphosphine)palladium(0), 24 mg of cuprous iodide and 1.1 ml of triethylamine, followed by heating under stirring at 60° C. in an oil bath for 1.3 hours in a nitrogen atmosphere. After cooling as it was, ethyl acetate and aqueous ammonia were added thereto and the mixture was extracted with ethyl acetate. The organic phase was further washed with brine, dried over anhydrous sodium sulfate and the solvent was removed. The residue was subjected to NH-silica gel column chromatography using 66% ethyl acetate/hexane and 2% methanol/ethyl acetate as eluents for separation and purification, to give 669 mg of the target compound.

Workup

  1. temperatureby heating
  2. temperatureAfter cooling as it
  3. extractionthe mixture was extracted with ethyl acetate
  4. washThe organic phase was further washed with brine
  5. dry with materialdried over anhydrous sodium sulfate
  6. customthe solvent was removed
  7. customfor separation and purification

Sources & evidence

ORD record
ord-49110aac6cd1485ea8665b6c0dc72f66
Source dataset
uspto-grants-2003_07
Patent number
US06599917B1

Reaction notes

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