Ethyl Acetate → ethyl 6-{[(3R)-1-benzyl-3-pyrrolidinyl]amino}-5-chloronicotinate

HRID 2375986Notes

Reaction equation

HRID 2375986 reaction equation
[Cl:1][C:2]1[C:3](Cl)=[N:4][CH:5]=[C:6]([CH:12]=1)[C:7]([O:9][CH2:10][CH3:11])=[O:8].[CH2:14]([N:21]1[CH2:25][CH2:24][C@@H:23]([NH2:26])[CH2:22]1)[C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1.C([O-])([O-])=O.[K+].[K+].CCOC(C)=O>CN(C=O)C.O>[CH2:14]([N:21]1[CH2:25][CH2:24][C@@H:23]([NH:26][C:3]2[C:2]([Cl:1])=[CH:12][C:6]([C:7]([O:9][CH2:10][CH3:11])=[O:8])=[CH:5][N:4]=2)[CH2:22]1)[C:15]1[CH:16]=[CH:17][CH:18]=[CH:19][CH:20]=1

Participants

7

Reactant 4

HCID 8857Ethyl AcetateHCID 11430Potassium CarbonateHCID 1519354(3R)-1-benzylpyrrolidin-3-amineHCID 16762519Ethyl 5,6-Dichloronicotinate

Product 1

HCID 68967686ethyl 6-{[(3R)-1-benzyl-3-pyrrolidinyl]amino}-5-chloronicotinateYield 97.5%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
100 °C

Procedure

A mixture of ethyl 5,6-dichloronicotinate (10.0 g), (3R)-(−)-1-benzyl-3-aminopyrrolidine (9.61 g), K2CO3 (8.38 g) and CuO (371 mg) 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-n-Hexane (7:3). The eluted fractions containing the desired product were collected and evaporated in vacuo to give ethyl 6-{[(3R)-1-benzyl-3-pyrrolidinyl]amino}-5-chloronicotinate (15.95 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-n-Hexane (7:3)
  6. additionThe eluted fractions containing the desired product
  7. customwere collected
  8. customevaporated in vacuo

Sources & evidence

ORD record
ord-d8b2198e33db4b249467886fd2b45271
Source dataset
uspto-grants-2008_12
Patent number
US07465731B2

Reaction notes

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