Potassium Iodide → Bisegliptin

HRID 606725Notes

Reaction equation

HRID 606725 reaction equation
Cl.[NH2:2][C:3]12[CH2:10][CH2:9][C:6]([C:11]([O:13][CH2:14][CH3:15])=[O:12])([CH2:7][CH2:8]1)[CH2:5][CH2:4]2.C(=O)([O-])[O-].[K+].[K+].[I-].[K+].[F:24][C@@H:25]1[CH2:29][N:28]([C:30](=[O:42])[CH2:31]OS(C2C=CC=CC=2)(=O)=O)[C@H:27]([C:43]#[N:44])[CH2:26]1>CN(C)C=O>[CH2:14]([O:13][C:11]([C:6]12[CH2:5][CH2:4][C:3]([NH:2][CH2:31][C:30]([N:28]3[CH2:29][C@@H:25]([F:24])[CH2:26][C@H:27]3[C:43]#[N:44])=[O:42])([CH2:10][CH2:9]1)[CH2:8][CH2:7]2)=[O:12])[CH3:15]

Participants

6

Reactant 4

HCID 4875Potassium IodideHCID 11430Potassium CarbonateHCID 24781881(2S,4S)-1-[2-(benzenesulfonyloxy)acetyl]-4-fluoropyrrolidine-2-carbonitrileHCID 66790102Ethyl 4-aminobicyclo[2.2.2]octane-1-carboxylate hydrochloride

Product 1

HCID 11688894BisegliptinYield 92.4%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

Ethyl 4-aminobicyclo[2.2.2]octane-1-carboxylate hydrochloride (206 mg), potassium carbonate (243.2 mg), potassium iodide (13.3 mg) and N,N-dimethylformamide (5 mL) were mixed together. To this mixture, a solution of (2S,4S)-4-fluoro-1-[2-(benzenesulfonyloxy)acetyl]pyrrolidine-2-carbonitrile (250 mg) in N,N-dimethylformamide (1.5 mL) was added at 50° C. and the mixture was further stirred for 1 hour. Subsequently, the reaction mixture was concentrated under reduced pressure and the residue was purified on a silica gel column (eluant=ethyl acetate:methanol=20:1) to give (2S,4S)-1-[2-[(4-ethoxycarbonylbicyclo[2.2.2]oct-1-yl)amino]ac etyl]-4-fluoropyrrolidine-2-carbonitrile as a white solid (260 mg, 92% yield).

Workup

  1. concentrationSubsequently, the reaction mixture was concentrated under reduced pressure
  2. customthe residue was purified on a silica gel column (eluant=ethyl acetate:methanol=20:1)

Sources & evidence

ORD record
ord-7f59168fad4344c3b1a4a42a21b863c9
Source dataset
uspto-grants-2011_03
Patent number
US07915427B2

Reaction notes

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