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

HRID 606730Notes

Reaction equation

HRID 606730 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+].C1(S(O[CH2:32][C:33]([N:35]2[CH2:39][C@@H:38]([F:40])[CH2:37][C@H:36]2[C:41]([NH2:43])=[O:42])=[O:34])(=O)=O)C=CC=CC=1>CN(C)C=O>[CH2:14]([O:13][C:11]([C:6]12[CH2:5][CH2:4][C:3]([NH:2][CH2:32][C:33]([N:35]3[CH2:39][C@@H:38]([F:40])[CH2:37][C@H:36]3[C:41]([NH2:43])=[O:42])=[O:34])([CH2:10][CH2:9]1)[CH2:8][CH2:7]2)=[O:12])[CH3:15]

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 24781877(2S,4S)-1-[2-(benzenesulfonyloxy)acetyl]-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 45%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Conditions

Temperature
45 °C

Procedure

Ethyl 4-aminobicyclo[2.2.2]octane-1-carboxylate hydrochloride (4.63 g), potassium carbonate (5.47 g) and N,N-dimethylformamide (40 mL) were mixed together. To this mixture, a solution of (2S,4S)-1-[2-(benzenesulfonyloxy)acetyl]-4-fluoropyrrolidine-2-carboxamide (5.93 g) in N,N-dimethylformamide (10 mL) was added at 40° C. and the mixture was stirred at 45° C. for 3 hours. Subsequently, the reaction mixture was concentrated under reduced pressure. Water (50 mL) was then added to the residue and the resulting crystal was collected by filtration, washed with water (30 mL), and dried at 50° C. under reduced pressure. The crude crystal was recrystallized from ethyl acetate (40 mL), washed with ethyl acetate (20 mL), and dried at room temperature under reduced pressure. This gave (2S,4S)-1-[2-[(4-ethoxycarbonylbicyclo[2.2.2]oct-1-yl)amino]ac etyl]-4-fluoropyrrolidine-2-carboxamide as a white solid in the form of colorless powder (1.81 g). The filtrate and the wash were combined and concentrated to 20 mL. The resulting crystal was collected by filtration, washed with a mixture of ethyl acetate and diisopropyl ether (1:1, 20 mL) to give additional 1.19 g of the product. The total amount of the product was 3.00 g (45% yield).

Workup

  1. concentrationSubsequently, the reaction mixture was concentrated under reduced pressure
  2. additionWater (50 mL) was then added to the residue
  3. filtrationthe resulting crystal was collected by filtration
  4. washwashed with water (30 mL)
  5. customdried at 50° C. under reduced pressure
  6. customThe crude crystal was recrystallized from ethyl acetate (40 mL)
  7. washwashed with ethyl acetate (20 mL)
  8. customdried at room temperature under reduced pressure
  9. concentrationconcentrated to 20 mL
  10. filtrationThe resulting crystal was collected by filtration
  11. washwashed with a mixture of ethyl acetate and diisopropyl ether (1:1, 20 mL)

Sources & evidence

ORD record
ord-69804196597545e5844e44d3ef2a0462
Source dataset
uspto-grants-2011_03
Patent number
US07915427B2

Reaction notes

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