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

HRID 2376115Notes

Reaction equation

HRID 2376115 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].[NH2:14][C@@H:15]1[CH2:19][CH2:18][N:17]([C:20]([O:22][C:23]([CH3:26])([CH3:25])[CH3:24])=[O:21])[CH2:16]1.C([O-])([O-])=O.[K+].[K+].CCOC(C)=O>CN(C=O)C.O>[C:23]([O:22][C:20]([N:17]1[CH2:18][CH2:19][C@@H:15]([NH:14][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)[CH2:16]1)=[O:21])([CH3:26])([CH3:24])[CH3:25]

Participants

7

Reactant 4

HCID 8857Ethyl AcetateHCID 11430Potassium CarbonateHCID 854070(R)-(+)-1-Boc-3-aminopyrrolidineHCID 16762519Ethyl 5,6-Dichloronicotinate

Product 1

HCID 68959254ethyl 6-{[(3R)-1-(tert-butoxycarbonyl)-3-pyrrolidinyl]amino}-5-chloronicotinateYield 78.5%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
100 °C

Procedure

A mixture of ethyl 5,6-dichloronicotinate (5.0 g), tert-butyl (3R)-3-amino-1-pyrrolidinecarboxylate (5.08 g) and K2CO3 (4.71 g) in DMF (40 ml) was stirred at 100° C. for 12 hours under atmospheric pressure of nitrogen. The reaction mixture was poured into a mixture of AcOEt and H2O 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 n-Hexane-AcOEt (9:1). The eluted fractions containing the desired product were collected and evaporated in vacuo to give ethyl 6-{[(3R)-1-(tert-butoxycarbonyl)-3-pyrrolidinyl]amino}-5-chloronicotinate (6.6 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 n-Hexane-AcOEt (9:1)
  6. additionThe eluted fractions containing the desired product
  7. customwere collected
  8. customevaporated in vacuo

Sources & evidence

ORD record
ord-64646d4e269d47b2aaf217658d588247
Source dataset
uspto-grants-2008_12
Patent number
US07465731B2

Reaction notes

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