Ethanol → Methyl 5-[3-(benzyloxy)-4-chlorophenyl]-6-oxo-1,6-dihydropyridine-3-carboxylate

HRID 1040356Notes

Reaction equation

HRID 1040356 reaction equation
I[C:2]1[C:7](=[O:8])[NH:6][CH:5]=[C:4]([C:9]([O:11][CH3:12])=[O:10])[CH:3]=1.[CH2:13]([O:20][C:21]1[CH:22]=[C:23](B2OC(C)(C)C(C)(C)O2)[CH:24]=[CH:25][C:26]=1[Cl:27])[C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1.CCO.C([O-])(O)=O.[Na+]>C(COC)OC.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]([O:20][C:21]1[CH:22]=[C:23]([C:2]2[C:7](=[O:8])[NH:6][CH:5]=[C:4]([C:9]([O:11][CH3:12])=[O:10])[CH:3]=2)[CH:24]=[CH:25][C:26]=1[Cl:27])[C:14]1[CH:15]=[CH:16][CH:17]=[CH:18][CH:19]=1

Participants

7

Reactant 4

HCID 702EthanolHCID 516892Sodium BicarbonateHCID 18525955Methyl 5-iodo-6-oxo-1,6-dihydropyridine-3-carboxylateHCID 598468812-(3-(Benzyloxy)-4-chlorophenyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane

Product 1

HCID 66720752Methyl 5-[3-(benzyloxy)-4-chlorophenyl]-6-oxo-1,6-dihydropyridine-3-carboxylate

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 80711,2-DimethoxyethaneSolvent

Conditions

Temperature
90 °C

Procedure

Stir a solution of 4 g (14.35 mmol) of methyl 5-iodo-6-oxo-1,6-dihydropyridine-3-carboxylate and 6.42 g (18.64 mmol) of 2-[3-(benzyloxy)-4-chlorophenyl]-4,4,5,5-tetramethyl-1,3,2-dioxaborolane in a mixture of 160 mL of dimethoxyethane (DME), 80 mL of EtOH and 120 mL of a saturated aqueous solution of NaHCO3 for 15 minutes under argon, then add 662 mg of Pd(PPh3)4 and heat the reaction mixture for 4 h 30 min at 90° C. After concentration under reduced pressure, distribute the residue obtained in a mixture of 200 mL of DCM and 10 mL of water. Extract the aqueous phase again with 100 mL of DCM, combine the organic phases, dry over MgSO4, filter and concentrate under reduced pressure. Purify the residue obtained by silica gel column chromatography, eluting with a DCM/methanol gradient from 0 to 2% of methanol. After concentration under reduced pressure, solidify the residue in a 5/95 methanol/ether mixture, then filter and wash with ether. We thus obtain 1.99 g of methyl 5-[3-(benzyloxy)-4-chlorophenyl]-6-oxo-1,6-dihydropyridine-3-carboxylate in the form of a beige solid.

Workup

  1. concentrationAfter concentration under reduced pressure
  2. customobtained in a mixture of 200 mL of DCM and 10 mL of water
  3. extractionExtract the aqueous phase again with 100 mL of DCM
  4. dry with materialdry over MgSO4
  5. filtrationfilter
  6. concentrationconcentrate under reduced pressure
  7. customPurify the residue
  8. customobtained by silica gel column chromatography
  9. washeluting with a DCM/methanol gradient from 0 to 2% of methanol
  10. concentrationAfter concentration under reduced pressure
  11. filtrationfilter
  12. washwash with ether

Sources & evidence

ORD record
ord-ffb49e1ebfc34d1fbc40a4319fd0fdc1
Source dataset
uspto-grants-2013_10
Patent number
US08552201B2

Reaction notes

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