Ethyl Acetate → methyl 6-{[(3R)-1-benzyl-3-pyrrolidinyl]amino}nicotinate

HRID 226299Notes

Reaction equation

HRID 226299 reaction equation
Cl[C:2]1[CH:11]=[CH:10][C:5]([C:6]([O:8][CH3:9])=[O:7])=[CH:4][N:3]=1.[CH2:12]([N:19]1[CH2:23][CH2:22][C@@H:21]([NH2:24])[CH2:20]1)[C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1.C([O-])([O-])=O.[K+].[K+].CCOC(C)=O>CN(C=O)C.O>[CH2:12]([N:19]1[CH2:23][CH2:22][C@@H:21]([NH:24][C:2]2[CH:11]=[CH:10][C:5]([C:6]([O:8][CH3:9])=[O:7])=[CH:4][N:3]=2)[CH2:20]1)[C:13]1[CH:14]=[CH:15][CH:16]=[CH:17][CH:18]=1

Participants

7

Reactant 4

HCID 8857Ethyl AcetateHCID 11430Potassium CarbonateHCID 254249Methyl 6-chloropyridine-3-carboxylateHCID 1519354(3R)-1-benzylpyrrolidin-3-amine

Product 1

HCID 68960481methyl 6-{[(3R)-1-benzyl-3-pyrrolidinyl]amino}nicotinateYield 68.2%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
100 °C

Procedure

A mixture of methyl 6-chloronicotinate (8.0 g), (3R)-(−)-1-benzyl-3-aminopyrrolidine (9.86 g), CuO (371 mg) and K2CO3 (8.38 g) in DMF (60 ml) was stirred at 100° C. for 10 hours under atmospheric pressure of nitrogen. The reaction mixture was poured into a mixture of AcOEt and water and the organic layer was washed with brine and dried over MgSO4. The solvent was evaporated in vacuo and the residue was chromatographed on silicagel eluting with AcOEt-MeOH (97:3). The eluted fractions containing the desired product were collected and evaporated in vacuo to give methyl 6-{[(3R)-1-benzyl-3-pyrrolidinyl]amino}nicotinate (9.9 g).

Workup

  1. washthe organic layer was washed with brine
  2. dry with materialdried over MgSO4
  3. customThe solvent was evaporated in vacuo
  4. customthe residue was chromatographed on silicagel
  5. washeluting with AcOEt-MeOH (97:3)
  6. additionThe eluted fractions containing the desired product
  7. customwere collected
  8. customevaporated in vacuo

Sources & evidence

ORD record
ord-0b7801fae5c7464889045bca4c81d6b0
Source dataset
uspto-grants-2009_07
Patent number
US07557127B2

Reaction notes

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