Sodium Methoxide → 3-[(1-Benzyl-8-hydroxy-2-oxo-1,2-dihydro-[1,6]naphthyridine-7-carbonyl)-amino]-2,2-dimethyl-propionic acid

HRID 919786Notes

Reaction equation

HRID 919786 reaction equation
CO[C:3]([C:5]1[C:14]([OH:15])=[C:13]2[C:8]([CH:9]=[CH:10][C:11](=[O:23])[N:12]2[CH2:16][C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)=[CH:7][N:6]=1)=[O:4].OC(C(F)(F)F)=O.[NH2:31][CH2:32][C:33]([CH3:38])([CH3:37])[C:34]([OH:36])=[O:35].C[O-].[Na+]>CCO.C([O-])(O)=O.[Na+]>[CH2:16]([N:12]1[C:13]2[C:8](=[CH:7][N:6]=[C:5]([C:3]([NH:31][CH2:32][C:33]([CH3:38])([CH3:37])[C:34]([OH:36])=[O:35])=[O:4])[C:14]=2[OH:15])[CH:9]=[CH:10][C:11]1=[O:23])[C:17]1[CH:18]=[CH:19][CH:20]=[CH:21][CH:22]=1

Participants

6

Reactant 3

HCID 10942334Sodium MethoxideHCID 682971941-Benzyl-8-hydroxy-2-oxo-1,2-dihydro-[1,6]naphthyridine-7-carboxylic acid methyl esterHCID 1317322153-Amino-2,2-dimethyl-propionic acid TFA salt

Product 1

HCID 682974623-[(1-Benzyl-8-hydroxy-2-oxo-1,2-dihydro-[1,6]naphthyridine-7-carbonyl)-amino]-2,2-dimethyl-propionic acidYield 27.8%

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 516892Sodium BicarbonateSolvent

Conditions

Temperature
150 °C

Procedure

A mixture of 1-benzyl-8-hydroxy-2-oxo-1,2-dihydro-[1,6]naphthyridine-7-carboxylic acid methyl ester (19 mg, 0.061 mmol), 3-amino-2,2-dimethyl-propionic acid TFA salt (71 mg, 0.31 mmol) and NaOMe (33 mg, 0.61 mmol) in 2 mL of EtOH was heated at 150° C. in a microwave reactor for 6 h. Solvent was evaporated in vacuo, and the residue was partitioned between water and EtOAc. 1 M was added with vigorous stirring until pH about 1. The organic layer was dried over MgSO4 and concentrated in vacuo. The crude product was purified by silica gel chromatography (5-60% EtOAc/hexanes+2% AcOH). The product isolated was then dissolved in saturated NaHCO3 and washed several times with ether. The aqueous layer was acidified to pH about 1 with 4 M HCl, and the resulting precipitate was collected by filtration and dried to give 6.7 mg of the title compound. MS: (+) m/z 396.30 (M+1).

Workup

  1. customSolvent was evaporated in vacuo
  2. customthe residue was partitioned between water and EtOAc
  3. addition1 M was added
  4. dry with materialThe organic layer was dried over MgSO4
  5. concentrationconcentrated in vacuo
  6. customThe crude product was purified by silica gel chromatography (5-60% EtOAc/hexanes+2% AcOH)
  7. customThe product isolated
  8. washwashed several times with ether
  9. filtrationthe resulting precipitate was collected by filtration
  10. customdried

Sources & evidence

ORD record
ord-f18368ba3b214dea835d675ab27de579
Source dataset
uspto-grants-2016_03
Patent number
US09271970B2

Reaction notes

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