Potassium Carbonate → (2S,4S)-1-[[(4-carbamoylbicyclo[2.2.2]oct-1-yl)amino]acetyl]-4-fluoropyrrolidine-2-carbonitrile

HRID 227937Notes

Reaction equation

HRID 227937 reaction equation
[NH2:1][C:2]12[CH2:9][CH2:8][C:5]([C:10]([NH2:12])=[O:11])([CH2:6][CH2:7]1)[CH2:4][CH2:3]2.C(=O)([O-])[O-].[K+].[K+].Br[CH2:20][C:21]([N:23]1[CH2:27][C@@H:26]([F:28])[CH2:25][C@H:24]1[C:29]#[N:30])=[O:22]>CN(C)C=O>[C:10]([C:5]12[CH2:4][CH2:3][C:2]([NH:1][CH2:20][C:21]([N:23]3[CH2:27][C@@H:26]([F:28])[CH2:25][C@H:24]3[C:29]#[N:30])=[O:22])([CH2:9][CH2:8]1)[CH2:7][CH2:6]2)(=[O:11])[NH2:12]

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 21090395(2S,4S)-1-(2-bromoacetyl)-4-fluoropyrrolidine-2-carbonitrileHCID 231505304-Aminobicyclo[2.2.2]octane-1-carboxamide

Product 1

HCID 11336237(2S,4S)-1-[[(4-carbamoylbicyclo[2.2.2]oct-1-yl)amino]acetyl]-4-fluoropyrrolidine-2-carbonitrileYield 98.2%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

4-Aminobicyclo[2.2.2]octane-1-carboxamide (50.0 mg) was dissolved in N,N-dimethylformamide (2 mL). To this solution, potassium carbonate (50.0 mg) was added, followed by dropwise addition of (2S,4S)-1-(2-bromoacetyl)-4-fluoropyrrolidine-2-carbonitrile (70.0 mg) in N,N-dimethylformamide (1 mL) at room temperature. The mixture was stirred at room temperature for 2.5 hours and was concentrated under reduced pressure. The resulting residue was purified by silica gel chromatography (eluant:chloroform:methanol=10:1) to give (2S,4S)-1-[[(4-carbamoylbicyclo[2.2.2]oct-1-yl)amino]acetyl]-4-fluoropyrrolidine-2-carbonitrile (94.1 mg).

Workup

  1. concentrationwas concentrated under reduced pressure
  2. customThe resulting residue was purified by silica gel chromatography (eluant:chloroform:methanol=10:1)

Sources & evidence

ORD record
ord-95e9291a90e644beb6ef72805a99c3ad
Source dataset
uspto-grants-2009_07
Patent number
US07560569B2

Reaction notes

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