Methyl 6-chloro-5'-methyl-3,3'-bipyridine-5-carboxylate → Methyl 6-cyclopentyl-5'-methyl-3,3'-bipyridine-5-carboxylate

HRID 1675946Notes

Reaction equation

HRID 1675946 reaction equation
Cl[C:2]1[N:7]=[CH:6][C:5]([C:8]2[CH:9]=[N:10][CH:11]=[C:12]([CH3:14])[CH:13]=2)=[CH:4][C:3]=1[C:15]([O:17][CH3:18])=[O:16].[Br-].[CH:20]1([Zn+])[CH2:24][CH2:23][CH2:22][CH2:21]1>O1CCOCC1.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[CH:20]1([C:2]2[N:7]=[CH:6][C:5]([C:8]3[CH:9]=[N:10][CH:11]=[C:12]([CH3:14])[CH:13]=3)=[CH:4][C:3]=2[C:15]([O:17][CH3:18])=[O:16])[CH2:24][CH2:23][CH2:22][CH2:21]1

Participants

5

Reactant 2

HCID 58539034Methyl 6-chloro-5'-methyl-3,3'-bipyridine-5-carboxylateHCID 178419768HCID 178419768, compound

Product 1

HCID 58539038Methyl 6-cyclopentyl-5'-methyl-3,3'-bipyridine-5-carboxylate

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
90 °C

Procedure

To a solution of methyl 6-chloro-5′-methyl-3,3′-bipyridine-5-carboxylate (6-1, 0.15 g, 0.57 mmol, 1.0 equiv, prepared in an analogous fashion to Examples 2 and 8) in dioxane (2.9 mL) at 25° C. was added cyclopentylzinc bromide (3.43 mL, 1.71 mmol, 3.0 equiv, 0.5 M in THF) and tetrakis(triphenylphosphine)palladium(0) (0.099 g, 0.086 mmol, 0.15 equiv). The reaction mixture was heated for 3 h at 90° C. The reaction mixture was cooled partitioned between water (10 mL) and EtOAc (30 mL), washed with water (3×30 mL) and brine (1×30 mL), and the organic phase was dried over magnesium sulfate. The residue was purified via normal phase chromatography (5 to 100% EtOAc in hexanes, silica) to afford the desired product (6-2) as an oil after concentration. ESI+MS [M+H]+ C18H20N2O2 calc'd 297.2, found 297.1

Workup

  1. temperatureThe reaction mixture was cooled
  2. custompartitioned between water (10 mL) and EtOAc (30 mL)
  3. washwashed with water (3×30 mL) and brine (1×30 mL)
  4. dry with materialthe organic phase was dried over magnesium sulfate
  5. customThe residue was purified via normal phase chromatography (5 to 100% EtOAc in hexanes, silica)

Sources & evidence

ORD record
ord-3addfc66213747f789ca3f2116139920
Source dataset
uspto-grants-2011_08
Patent number
US08003797B2

Reaction notes

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