Ammonium formate → (2S,4S)-1-[[N-[4-(piperidin-1-yl)carbonylbicyclo[2.2.2]oct-1-yl]amino]acetyl]-4-fluoropyrrolidine-2-carbonitrile

HRID 227943Notes

Reaction equation

HRID 227943 reaction equation
C(OC([N:11]([CH2:28][C:29]([N:31]1[CH2:35][C@@H:34]([F:36])[CH2:33][C@H:32]1[C:37]#[N:38])=[O:30])[C:12]12[CH2:19][CH2:18][C:15]([C:20]([N:22]3[CH2:27][CH2:26][CH2:25][CH2:24][CH2:23]3)=[O:21])([CH2:16][CH2:17]1)[CH2:14][CH2:13]2)=O)C1C=CC=CC=1.C([O-])=O.[NH4+]>CN(C)C=O.[C].[Pd]>[N:22]1([C:20]([C:15]23[CH2:14][CH2:13][C:12]([NH:11][CH2:28][C:29]([N:31]4[CH2:35][C@@H:34]([F:36])[CH2:33][C@H:32]4[C:37]#[N:38])=[O:30])([CH2:19][CH2:18]2)[CH2:17][CH2:16]3)=[O:21])[CH2:27][CH2:26][CH2:25][CH2:24][CH2:23]1

Participants

5

Reactant 2

HCID 2723923Ammonium formateHCID 68844891(2S,4S)-1-[[N-benzyloxycarbonyl-N-[4-(piperidin-1-yl)carbonylbicyclo[2.2.2]oct-1-yl]amino]acetyl]-4-fluoropyrrolidine-2-carbonitrile

Product 1

HCID 57756780(2S,4S)-1-[[N-[4-(piperidin-1-yl)carbonylbicyclo[2.2.2]oct-1-yl]amino]acetyl]-4-fluoropyrrolidine-2-carbonitrileYield 88.7%

Reagents, catalysts & solvents 2

HCID 178418390HCID 178418390, compoundCatalystHCID 6228DimethylformamideSolvent

Procedure

(2S,4S)-1-[[N-Benzyloxycarbonyl-N-[4-(piperidin-1-yl)carbonylbicyclo[2.2.2]oct-1-yl]amino]acetyl]-4-fluoropyrrolidine-2-carbonitrile (20.0 mg) and 10% palladium carbon (12.0 mg) were dissolved in dimethylformamide (0.5 mL). While the solution was chilled in an ice bath, ammonium formate (43.1 mg) was added and the mixture was stirred for 40 minutes at the same temperature. Subsequently, the reaction mixture was filtered through a Celite pad and diluted with ethyl acetate. The organic layer washed sequentially with water and saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The resulting residue was purified by column chromatography (eluant:dichloromethane:methanol=10:1) to give (2S,4S)-1-[[N-[4-(piperidin-1-yl)carbonylbicyclo[2.2.2]oct-1-yl]amino]acetyl]-4-fluoropyrrolidine-2-carbonitrile (13.2 mg).

Workup

  1. temperatureWhile the solution was chilled in an ice bath
  2. filtrationSubsequently, the reaction mixture was filtered through a Celite pad
  3. additiondiluted with ethyl acetate
  4. washThe organic layer washed sequentially with water and saturated brine
  5. dry with materialdried over anhydrous sodium sulfate
  6. concentrationconcentrated under reduced pressure
  7. customThe resulting residue was purified by column chromatography (eluant:dichloromethane:methanol=10:1)

Sources & evidence

ORD record
ord-5928b10f5afa4f4fa22ff4742e663e73
Source dataset
uspto-grants-2009_07
Patent number
US07560569B2

Reaction notes

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