Trifluoroacetic anhydride → Bisegliptin

HRID 606731Notes

Reaction equation

HRID 606731 reaction equation
FC(F)(F)C(OC(=O)C(F)(F)F)=O.[CH2:14]([O:16][C:17]([C:19]12[CH2:26][CH2:25][C:22]([NH:27][CH2:28][C:29]([N:31]3[CH2:35][C@@H:34]([F:36])[CH2:33][C@H:32]3[C:37]([NH2:39])=O)=[O:30])([CH2:23][CH2:24]1)[CH2:21][CH2:20]2)=[O:18])[CH3:15].C(=O)(O)[O-].[Na+]>O1CCCC1>[CH2:14]([O:16][C:17]([C:19]12[CH2:26][CH2:25][C:22]([NH:27][CH2:28][C:29]([N:31]3[CH2:35][C@@H:34]([F:36])[CH2:33][C@H:32]3[C:37]#[N:39])=[O:30])([CH2:23][CH2:24]1)[CH2:21][CH2:20]2)=[O:18])[CH3:15]

Participants

5

Reactant 3

HCID 9845Trifluoroacetic anhydride2×HCID 516892Sodium BicarbonateHCID 46854534(2S,4S)-1-[2-[(4-ethoxycarbonylbicyclo[2.2.2]oct-1-yl)amino]acetyl]-4-fluoropyrrolidine-2-carboxamide

Product 1

HCID 11688894BisegliptinYield 67%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

Trifluoroacetic anhydride (80 μL) was added to a solution of (2S,4S)-1-[2-[(4-ethoxycarbonylbicyclo[2.2.2]oct-1-yl)amino]ac etyl]-4-fluoropyrrolidine-2-carboxamide (100 mg) in tetrahydrofuran (1 mL). The mixture was stirred at room temperature for 2 hours and then at 40° C. for 1.5 hours. Subsequently, additional trifluoroacetic anhydride (40 μL) was added and the mixture was further stirred for 30 minutes. A saturated aqueous sodium bicarbonate solution (5 mL) was then added and the reaction mixture was extracted with ethyl acetate (2×10 mL). The ethyl acetate extracts were combined, washed with saturated brine (5 mL), dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The resulting residue was purified on an aminated silica gel column (eluant=ethyl acetate:methanol=30:1) to give (2S,4S)-1-[2-[(4-ethoxycarbonylbicyclo[2.2.2]oct-1-yl)amino]ac etyl]-4-fluoropyrrolidine-2-carbonitrile as a colorless solid (63.7 mg, 67% yield). This compound was identical to the compound obtained in Example 7.

Workup

  1. waitat 40° C. for 1.5 hours
  2. stirringthe mixture was further stirred for 30 minutes
  3. extractionthe reaction mixture was extracted with ethyl acetate (2×10 mL)
  4. washwashed with saturated brine (5 mL)
  5. dry with materialdried over anhydrous sodium sulfate
  6. concentrationconcentrated under reduced pressure
  7. customThe resulting residue was purified on an aminated silica gel column (eluant=ethyl acetate:methanol=30:1)

Sources & evidence

ORD record
ord-9f7ece6d8e6d43e9a461493dd80fc73c
Source dataset
uspto-grants-2011_03
Patent number
US07915427B2

Reaction notes

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