Potassium Iodide → (2S,4S)-1-[2-[(4-ethoxycarbonylbicyclo[2.2.2]oct-1-yl)amino]acetyl]-4-fluoropyrrolidine-2-carboxamide

HRID 1099382Notes

Reaction equation

HRID 1099382 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+].Cl[CH2:25][C:26]([N:28]1[CH2:32][C@@H:31]([F:33])[CH2:30][C@H:29]1[C:34]([NH2:36])=[O:35])=[O:27]>O.CN(C)C=O>[CH2:14]([O:13][C:11]([C:6]12[CH2:5][CH2:4][C:3]([NH:2][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:35])=[O:27])([CH2:10][CH2:9]1)[CH2:8][CH2:7]2)=[O:12])[CH3:15]

Participants

7

Reactant 4

HCID 4875Potassium IodideHCID 11430Potassium CarbonateHCID 45081036(2S,4S)-1-(2-chloroacetyl)-4-fluoropyrrolidine-2-carboxamideHCID 66790102Ethyl 4-aminobicyclo[2.2.2]octane-1-carboxylate hydrochloride

Product 1

HCID 46854534(2S,4S)-1-[2-[(4-ethoxycarbonylbicyclo[2.2.2]oct-1-yl)amino]acetyl]-4-fluoropyrrolidine-2-carboxamideYield 74%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

Ethyl 4-aminobicyclo[2.2.2]octane-1-carboxylate hydrochloride (68.8 g), potassium carbonate (77.6 g), potassium iodide (46.6 g) and N,N-dimethylformamide (167 mL) were mixed, and (2S,4S)-1-(chloroacetyl)-4-fluoropyrrolidine-2-carboxamide (55.8 g) was added dropwise thereto for 6 hours, while stirring at room temperature. After further stirring at the same temperature for 1 hour, water (1400 mL) was added to the reaction solution, followed by stirring at an inner temperature of 10° C. or lower for 1 hour. The precipitate were collected by filtration, washed with cold water (279 mL) and then dried under a reduced pressure at an outer temperature of 60° C., thereby obtaining white crystals of (2S,4S)-1-[2-[(4-ethoxycarbonylbicyclo[2.2.2]oct-1-yl)amino]acetyl]-4-fluoropyrrolidine-2-carboxamide (obtained amount: 72.9 g, yield: 74%).

Workup

  1. stirringAfter further stirring at the same temperature for 1 hour
  2. stirringby stirring at an inner temperature of 10° C. or lower for 1 hour
  3. filtrationThe precipitate were collected by filtration
  4. washwashed with cold water (279 mL)
  5. customdried under a reduced pressure at an outer temperature of 60° C.

Sources & evidence

ORD record
ord-a68e0fd175e745949b01760e83979d0d
Source dataset
uspto-grants-2012_03
Patent number
US08143427B2

Reaction notes

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