Methyl 2-chloropyridine-4-carboxylate → Methyl 2-benzylisonicotinate

HRID 1963125Notes

Reaction equation

HRID 1963125 reaction equation
Cl[C:2]1[CH:3]=[C:4]([CH:9]=[CH:10][N:11]=1)[C:5]([O:7][CH3:8])=[O:6].[Br-].[CH2:13]([Zn+])[C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1>C1COCC1.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>[CH2:13]([C:2]1[CH:3]=[C:4]([CH:9]=[CH:10][N:11]=1)[C:5]([O:7][CH3:8])=[O:6])[C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1

Participants

5

Reactant 2

HCID 2736842Methyl 2-chloropyridine-4-carboxylateHCID 178419772HCID 178419772, compound

Product 1

HCID 66731507Methyl 2-benzylisonicotinate

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
60 °C

Procedure

Methyl 2-chloroisonicotinate (4.29 g, 25 mmol) and Pd(PPh3)4 (1.156 g, 1.00 mmol) were dissolved in THF (60 mL) to give a yellow solution. Then benzylzinc(II) bromide (0.5 M in THF) (75 mL, 37.50 mmol) was added. The resulting brown mixture was warmed to 60° C. in an oil-bath for 18 h. The reaction mixture was quenched by addition of methanol, then diluted with ethyl acetate and washed with satd NH4Cl and water. The combined organic layers were dried over MgSO4 and evaporated. The residue was purified via Biotage, Thompsson 160 g Silica, eluent isocratic heptanes/ethyl acetate 9:1 over 1 CV, then linear gradient 9:1-75:25 over 6 CV. Product containing fractions were evaporated to give methyl 2-benzylisonicotinate as an orange liquid. 1H NMR (400 MHz, cdcl3) δ 3.91 (s, 3H), 4.22 (s, 2H), 7.19-7.34 (m, 5H), 7.66 (dd, 1H), 7.69 (d, 1H), 8.70 (d, 1H).

Workup

  1. customto give a yellow solution
  2. customThe reaction mixture was quenched by addition of methanol
  3. additiondiluted with ethyl acetate
  4. washwashed with satd NH4Cl and water
  5. dry with materialThe combined organic layers were dried over MgSO4
  6. customevaporated
  7. customThe residue was purified via Biotage, Thompsson 160 g Silica, eluent isocratic heptanes/ethyl acetate 9:1 over 1 CV
  8. additionProduct containing fractions
  9. customwere evaporated

Sources & evidence

ORD record
ord-dc2f6d101b7443d3bbf78bdf86445b0e
Source dataset
uspto-grants-2013_04
Patent number
US08415378B2

Reaction notes

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