Potassium Carbonate → 5-[2-(4-Methoxybenzylamino)pyridin-6-yl]pentanoic acid ethyl ester

HRID 2187396Notes

Reaction equation

HRID 2187396 reaction equation
[C:1]([O:7][CH2:8][CH3:9])(=[O:6])[CH2:2][CH2:3][CH:4]=[CH2:5].B1C2CCCC1CCC2.Br[C:20]1[CH:25]=[CH:24][CH:23]=[C:22]([NH:26][CH2:27][C:28]2[CH:33]=[CH:32][C:31]([O:34][CH3:35])=[CH:30][CH:29]=2)[N:21]=1.C([O-])([O-])=O.[K+].[K+]>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>[CH2:8]([O:7][C:1](=[O:6])[CH2:2][CH2:3][CH2:4][CH2:5][C:20]1[N:21]=[C:22]([NH:26][CH2:27][C:28]2[CH:29]=[CH:30][C:31]([O:34][CH3:35])=[CH:32][CH:33]=2)[CH:23]=[CH:24][CH:25]=1)[CH3:9]

Participants

8

Reactant 4

HCID 11430Potassium CarbonateHCID 74786Ethyl 4-pentenoateHCID 789669-Borabicyclo(3.3.1)nonaneHCID 234355096-Bromo-(4-methoxybenzylamino)pyridine

Product 1

HCID 700925705-[2-(4-Methoxybenzylamino)pyridin-6-yl]pentanoic acid ethyl ester

Reagents, catalysts & solvents 3

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

Procedure

Ethyl 4-pentenoate (8.95 g, 69.8 mmol) was treated with 9-BBN (167 mL, 83.7 mmol; 0.5M in THF) at 0° C. then warmed to room temperature and stirred for 16 hours. To this solution was added Pd(OAc)2 (1.57 g, 6.98 mmol), pyridine 16-2 (18.4 g, 62.8 mmol), K2CO3 (14.4 g, 105 mmol), 1,1′-bis(diphenylphosphino)-ferrocene (3.87 g, 6.98 mmol) and DMF (200 mL). The mixture was degassed with argon for 10 minutes then heated to 80° C. for 24 hours. The reaction mixture was cooled and stirred with ethanolamine (20 mL) for 2 hours. The mixture was partitioned between water and EtOAc, extracted with EtOAc (3×), washed with water (3×), then brine, dried (MgSO4) and concentrated. Purification by silica gel chromatography (hexane:EtOAc 3:2) afforded the title compound 16-3 as an oil.

Workup

  1. customThe mixture was degassed with argon for 10 minutes
  2. temperaturethen heated to 80° C. for 24 hours
  3. temperatureThe reaction mixture was cooled
  4. stirringstirred with ethanolamine (20 mL) for 2 hours
  5. customThe mixture was partitioned between water and EtOAc
  6. extractionextracted with EtOAc (3×)
  7. washwashed with water (3×)
  8. dry with materialbrine, dried (MgSO4)
  9. concentrationconcentrated
  10. customPurification by silica gel chromatography (hexane:EtOAc 3:2)

Sources & evidence

ORD record
ord-6353939ef3c349538151aeb37fa94ff8
Source dataset
uspto-grants-2002_06
Patent number
US06410526B1

Reaction notes

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