Benzyl Bromide → Methyl 1-benzyl-4-(benzyloxy)-2-oxo-1,2-dihydro-1,5-naphthyridine-3-carboxylate

HRID 1179325Notes

Reaction equation

HRID 1179325 reaction equation
[Na].[OH:2][C:3]1[C:12]2[C:7](=[CH:8][CH:9]=[CH:10][N:11]=2)[NH:6][C:5](=[O:13])[C:4]=1[C:14]([O:16][CH3:17])=[O:15].[CH2:18](Br)[C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1>O.C(Cl)Cl.[Br-].C([N+](CCCC)(CCCC)CCCC)CCC>[CH2:18]([N:6]1[C:7]2[C:12](=[N:11][CH:10]=[CH:9][CH:8]=2)[C:3]([O:2][CH2:18][C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=2)=[C:4]([C:14]([O:16][CH3:17])=[O:15])[C:5]1=[O:13])[C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1

Participants

7

Reactant 3

HCID 7498Benzyl BromideHCID 5360545SodiumHCID 54729994Methyl 4-Hydroxy-2-oxo-1,2-dihydro-1,5-naphthyridine-3-carboxylate

Product 1

HCID 58977987Methyl 1-benzyl-4-(benzyloxy)-2-oxo-1,2-dihydro-1,5-naphthyridine-3-carboxylate

Reagents, catalysts & solvents 3

HCID 74236Tetrabutylammonium BromideCatalystHCID 962WaterSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
50 °C

Procedure

To a solution of the sodium salt of methyl 4-hydroxy-2-oxo-1,2-dihydro-1,5-naphthyridine-3-carboxylate (2.0 g, 7.57 mmol) in water (50 mL) was added a solution of benzyl bromide (3.89 g, 22.72 mmol) in methylene chloride (50 mL). To the biphasic solution was then added tetrabutylammonium bromide (1.2 g, 3.79 mmol) and the reaction was sealed and heated to 50° C. After stirring overnight the reactions was cooled and the two layers were separated. The aqueous layer was extracted one time with methylene chloride and the combined organics were dried over sodium sulfate, filtered and concentrated. The crude mixture was separated by normal phase chromatography using an Isco 120 gram silica gel cartridge with a 50 minute gradient running at 40 mL/min. of 10% to 60% EtOAc/hexanes. The tubes containing the desired product were concentrated and taken on to the next step.

Workup

  1. temperaturewas cooled
  2. customthe two layers were separated
  3. extractionThe aqueous layer was extracted one time with methylene chloride
  4. dry with materialthe combined organics were dried over sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe crude mixture was separated by normal phase chromatography
  8. customwith a 50 minute
  9. additionThe tubes containing the desired product
  10. concentrationwere concentrated

Sources & evidence

ORD record
ord-8d4c5bb30e484886b8afc49941b5e28c
Source dataset
uspto-grants-2007_10
Patent number
US07279487B2

Reaction notes

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