Water → Bisegliptin

HRID 1099389Notes

Reaction equation

HRID 1099389 reaction equation
C1(S(O)(=O)=O)C=CC=CC=1.[CH2:11]([O:13][C:14]([C:16]12[CH2:23][CH2:22][C:19]([NH:24][CH2:25][C:26]([N:28]3[CH2:32][C@@H:31]([F:33])[CH2:30][C@H:29]3[C:34]([NH2:36])=O)=[O:27])([CH2:20][CH2:21]1)[CH2:18][CH2:17]2)=[O:15])[CH3:12].FC(F)(F)C(OC(=O)C(F)(F)F)=O.O.C(=O)([O-])[O-].[K+].[K+]>CN(C)C=O>[CH2:11]([O:13][C:14]([C:16]12[CH2:23][CH2:22][C:19]([NH:24][CH2:25][C:26]([N:28]3[CH2:32][C@@H:31]([F:33])[CH2:30][C@H:29]3[C:34]#[N:36])=[O:27])([CH2:20][CH2:21]1)[CH2:18][CH2:17]2)=[O:15])[CH3:12]

Participants

6

Reactant 4

HCID 962WaterHCID 9845Trifluoroacetic anhydrideHCID 11430Potassium CarbonateHCID 46854533HCID 46854533, compound

Product 1

HCID 11688894BisegliptinYield 84%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

(2S,4S)-1-[2-[(4-Ethoxycarbonylbicyclo[2.2.2]-oct-1-yl)amino]acetyl]-4-fluoropyrrolidine-2-carboxamide benzenesulfonate (791 mg) was suspended in N,N-dimethylformamide (2.8 mL), and trifluoroacetic acid anhydride (0.22 mL) was added thereto, followed by stirring under ice-cooling for 1 hour. After adding water (14 mL), potassium carbonate (644 mg) was added thereto at a bath temperature of 40° C., followed by ice-cooling and 1 hour of stirring. The precipitate were collected by filtration, washed with water (3 mL) and then blast-dried at 60° C., thereby obtaining a white powder of (2S,4S)-1-[2-[(4-ethoxycarbonylbicyclo[2.2.2]oct-1-yl)amino]acetyl]-4-fluoropyrrolidine-2-carbonitrile (441 mg, 84%).

Workup

  1. temperaturecooling for 1 hour
  2. additionwas added
  3. customat a bath temperature of 40° C., followed by ice-
  4. temperaturecooling and 1 hour
  5. stirringof stirring
  6. filtrationThe precipitate were collected by filtration
  7. washwashed with water (3 mL)
  8. customblast-dried at 60° C.

Sources & evidence

ORD record
ord-9061e2f11245434cadfe599d35f1effa
Source dataset
uspto-grants-2012_03
Patent number
US08143427B2

Reaction notes

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