Hydrochloric Acid → 1,3-Dibenzyl-5-hydroxy-2-oxo-1,2-dihydro-[1,7]naphthyridine-6-carboxylic acid methyl ester

HRID 1410664Notes

Reaction equation

HRID 1410664 reaction equation
[CH3:1][O:2][C:3]([C:5]1[C:6]([OH:24])=[C:7]2[C:12](=[CH:13][N:14]=1)[N:11]([CH2:15][C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1)[C:10](=[O:22])[C:9](Br)=[CH:8]2)=[O:4].[Br-].[CH2:26]([Zn+])[C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=1.Cl.CCOC(C)=O>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>[CH3:1][O:2][C:3]([C:5]1[C:6]([OH:24])=[C:7]2[C:12](=[CH:13][N:14]=1)[N:11]([CH2:15][C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1)[C:10](=[O:22])[C:9]([CH2:26][C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=1)=[CH:8]2)=[O:4]

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 8857Ethyl AcetateHCID 682974771-Benzyl-3-bromo-5-hydroxy-2-oxo-1,2-dihydro-[1,7]naphthyridine-6-carboxylic acid methyl esterHCID 178419772HCID 178419772, compound

Product 1

HCID 682973641,3-Dibenzyl-5-hydroxy-2-oxo-1,2-dihydro-[1,7]naphthyridine-6-carboxylic acid methyl esterYield 57%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 8028TetrahydrofuranSolvent

Procedure

A mixture of 1-benzyl-3-bromo-5-hydroxy-2-oxo-1,2-dihydro-[1,7]naphthyridine-6-carboxylic acid methyl ester (800 mg, 2.06 mmol), benzylzinc bromide (10.3 mL, 5.14 mmol, 0.5 M in THF), and Pd(PPh3)4 (238 mg, 0.206 mmol) in THF (20 mL) was refluxed under nitrogen atmosphere for 16 h. After the mixture was cooled to r.t., 1 M HCl and EtOAc were added. The aqueous layer was extracted with additional EtOAc, and the combined organic layer was dried over MgSO4. After evaporating the solvent in vacuo, the crude product was chromatographed (0-40% EtOAc/hexanes+2% AcOH) to give 470 mg of the title compound as a yellow solid. MS: (+) m/z 401.12 (M+1).

Workup

  1. temperaturewas refluxed under nitrogen atmosphere for 16 h
  2. extractionThe aqueous layer was extracted with additional EtOAc
  3. dry with materialthe combined organic layer was dried over MgSO4
  4. customAfter evaporating the solvent in vacuo
  5. customthe crude product was chromatographed (0-40% EtOAc/hexanes+2% AcOH)

Sources & evidence

ORD record
ord-14ecd90a39cd489a812a805308d92191
Source dataset
uspto-grants-2014_12
Patent number
US08921389B2

Reaction notes

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