Potassium Carbonate → Ethyl 5-(4-chloro-3-methyl-[1,8]-naphthyridin-2-yl)pentanoate

HRID 2187379Notes

Reaction equation

HRID 2187379 reaction equation
[C:1]([O:7][CH2:8][CH3:9])(=[O:6])[CH2:2][CH2:3][CH:4]=[CH2:5].B1C2CCCC1CCC2.C([O-])([O-])=O.[K+].[K+].Cl[C:26]1[C:35]([CH3:36])=[C:34]([Cl:37])[C:33]2[C:28](=[N:29][CH:30]=[CH:31][CH:32]=2)[N:27]=1>C1COCC1.CC([O-])=O.CC([O-])=O.[Pd+2].C1(P(C2C=CC=CC=2)[C-]2C=CC=C2)C=CC=CC=1.[C-]1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=C1.[Fe+2].CN(C=O)C>[Cl:37][C:34]1[C:33]2[C:28](=[N:29][CH:30]=[CH:31][CH:32]=2)[N:27]=[C:26]([CH2:5][CH2:4][CH2:3][CH2:2][C:1]([O:7][CH2:8][CH3:9])=[O:6])[C:35]=1[CH3:36]

Participants

9

Reactant 4

HCID 11430Potassium CarbonateHCID 74786Ethyl 4-pentenoateHCID 789669-Borabicyclo(3.3.1)nonaneHCID 220826612,4-Dichloro-3-methyl-1,8-naphthyridine

Product 1

HCID 18475432Ethyl 5-(4-chloro-3-methyl-[1,8]-naphthyridin-2-yl)pentanoate

Reagents, catalysts & solvents 4

HCID 167845palladium(II) acetateCatalystHCID 635956Ferrocene-1,1'-bis-(diphenylphosphine)CatalystHCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
75 °C

Procedure

To a solution of ethyl 4-pentenoate (2.5 g, 20 mmol) in 60 mL THF was added 9-BBN (0.5 M in THF, 47 mL, 23 mmol) gradually at room temperature. After stirring for 10 hours, it was treated with Pd(OAc)2 (0.4 g, 2.0 mmol), 1,1′-bis(diphenylphosphino)-ferrocene (DPPF) (1.1 g, 2.0 mmol), K2CO3 (powder, 8.1 g, 58 mmol), 2,4-dichloro-3-methyl-naphthyridine (L) (3.6 g, 20 mmol) and 50 mL DMF. The reaction mixture was purged with argon for 5 minutes and then refluxed at 75° C. for 24 hours. It was cooled to room temperature and treated with 10 mL ethanolamine and stirred for 30 minutes. The mixture was diluted with 400 mL H2O and extracted with EtOAc(×3). The combined organic layers were washed with brine and dried. After solvent removal, the residue was purified by silica gel chromatography using EtOAc/hexanes (1:1) to give the desired product 3-3 as a liquid.

Workup

  1. customThe reaction mixture was purged with argon for 5 minutes
  2. temperatureIt was cooled to room temperature
  3. additiontreated with 10 mL ethanolamine
  4. stirringstirred for 30 minutes
  5. additionThe mixture was diluted with 400 mL H2O
  6. extractionextracted with EtOAc(×3)
  7. washThe combined organic layers were washed with brine
  8. customdried
  9. customAfter solvent removal
  10. customthe residue was purified by silica gel chromatography

Sources & evidence

ORD record
ord-f61ba7ed573a42e384bb8cb7db67a911
Source dataset
uspto-grants-2002_06
Patent number
US06410526B1

Reaction notes

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