Ammonium formate → ethyl 6-{[(3R)-1-benzyl-3-pyrrolidinyl]amino}-5-fluoronicotinate

HRID 226451Notes

Reaction equation

HRID 226451 reaction equation
[CH2:1]([N:8]1[CH2:12][CH2:11][C@@H:10]([NH:13][C:14]2[C:24]([F:25])=[CH:23][C:17]([C:18]([O:20][CH2:21][CH3:22])=[O:19])=[C:16](Cl)[N:15]=2)[CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C([O-])=O.[NH4+]>C(O)C.[Pd]>[CH2:1]([N:8]1[CH2:12][CH2:11][C@@H:10]([NH:13][C:14]2[C:24]([F:25])=[CH:23][C:17]([C:18]([O:20][CH2:21][CH3:22])=[O:19])=[CH:16][N:15]=2)[CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

5

Reactant 2

HCID 2723923Ammonium formateHCID 86603759ethyl 6-{[(3R)-1-benzyl-3-pyrrolidinyl]amino}-2-chloro-5-fluoronicotinate

Product 1

HCID 68963376ethyl 6-{[(3R)-1-benzyl-3-pyrrolidinyl]amino}-5-fluoronicotinateYield 66.5%

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 702EthanolSolvent

Procedure

To a solution of ethyl 6-{[(3R)-1-benzyl-3-pyrrolidinyl]amino}-2-chloro-5-fluoronicotinate (500 mg) in ethanol (20 mL) were added ammonium formate (584 mg) and 10% Pd/C (300 mg) at 25° C. and the mixture was heated to reflux with stirring for 1 hour. After cooling, the catalyst in the reaction mixture was removed by filtration. The filtrate was evaporated in vacuo. To the residue were added CH2Cl2(30 ml), ethanol (7 mL), and benzaldehyde (140 mg) at 25° C. After stirring for 5 minutes, sodium triacetoxyborohydride (280 mg) was 3 hours, and then poured into a mixture of CH2Cl2 and aqueous NaHCO3. The organic layer was separated, dried over sodium sulfate, and concentrated in vacuo. The residue was purified by column chromatography on silica gel (11 g) using a mixed solvent of dichloromethane and MeOH (100:1 to 40:1). The fractions containing the objective compound were collected and evaporated under reduced pressure. Title compound (302 mg, 66%) was obtained as colorless syrup.

Workup

  1. temperaturethe mixture was heated
  2. temperatureto reflux
  3. temperatureAfter cooling
  4. customthe catalyst in the reaction mixture was removed by filtration
  5. customThe filtrate was evaporated in vacuo
  6. additionTo the residue were added CH2Cl2(30 ml), ethanol (7 mL), and benzaldehyde (140 mg) at 25° C
  7. stirringAfter stirring for 5 minutes
  8. waitsodium triacetoxyborohydride (280 mg) was 3 hours
  9. additionpoured into a mixture of CH2Cl2 and aqueous NaHCO3
  10. customThe organic layer was separated
  11. dry with materialdried over sodium sulfate
  12. concentrationconcentrated in vacuo
  13. customThe residue was purified by column chromatography on silica gel (11 g)
  14. additionThe fractions containing the objective compound
  15. customwere collected
  16. customevaporated under reduced pressure

Sources & evidence

ORD record
ord-5aed6f5ddbb2440b9689024c388f3464
Source dataset
uspto-grants-2009_07
Patent number
US07557127B2

Reaction notes

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