Potassium Carbonate → (2S,4S)-1-[[N-(4-ethoxycarbonylbicyclo[2.2.1]hept-1-yl)amino]acetyl]-4-fluoropyrrolidine-2-carbonitrile

HRID 2355178Notes

Reaction equation

HRID 2355178 reaction equation
[NH2:1][C:2]12[CH2:8][C:5]([C:9]([O:11][CH2:12][CH3:13])=[O:10])([CH2:6][CH2:7]1)[CH2:4][CH2:3]2.C(=O)([O-])[O-].[K+].[K+].Br[CH2:21][C:22]([N:24]1[CH2:28][C@@H:27]([F:29])[CH2:26][C@H:25]1[C:30]#[N:31])=[O:23]>CN(C)C=O>[CH2:12]([O:11][C:9]([C:5]12[CH2:8][C:2]([NH:1][CH2:21][C:22]([N:24]3[CH2:28][C@@H:27]([F:29])[CH2:26][C@H:25]3[C:30]#[N:31])=[O:23])([CH2:3][CH2:4]1)[CH2:7][CH2:6]2)=[O:10])[CH3:13]

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 21090395(2S,4S)-1-(2-bromoacetyl)-4-fluoropyrrolidine-2-carbonitrileHCID 23149671Ethyl 4-aminobicyclo[2.2.1]heptane-1-carboxylate

Product 1

HCID 59383143(2S,4S)-1-[[N-(4-ethoxycarbonylbicyclo[2.2.1]hept-1-yl)amino]acetyl]-4-fluoropyrrolidine-2-carbonitrileYield 96.7%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

Ethyl 4-aminobicyclo[2.2.1]heptane-1-carboxylate (50.0 mg) was dissolved in N,N-dimethylformamide (2 mL) and potassium-carbonate (40.0 mg) was added to the solution. (2S,4S)-1-(2-Bromoacetyl)-4-fluoropyrrolidine-2-carbonitrile (64.2 mg) in N,N-dimethylformamide (1 mL) was then added dropwise at room temperature and the mixture was stirred for 1 hour. The insoluble materials were filtered and the filtrate was concentrated. The resulting residue was purified by silica gel column chromatography (NH silica, eluant: ethyl acetate) to give (2S,4S)-1-[[N-(4-ethoxycarbonylbicyclo[2.2.1]hept-1-yl)amino]acetyl]-4-fluoropyrrolidine-2-carbonitrile (89.0 mg).

Workup

  1. filtrationThe insoluble materials were filtered
  2. concentrationthe filtrate was concentrated
  3. customThe resulting residue was purified by silica gel column chromatography (NH silica, eluant: ethyl acetate)

Sources & evidence

ORD record
ord-8192175d802845e8a3f7ae1aa99891b7
Source dataset
uspto-grants-2010_07
Patent number
US07754757B2

Reaction notes

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