Lithium hydroxide, monohydrate → HCID 90272154, compound

HRID 1497683Notes

Reaction equation

HRID 1497683 reaction equation
[C:1]1([C:25]2[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=2)[CH:6]=[CH:5][CH:4]=[CH:3][C:2]=1[CH2:7][N:8]1[C:17]2[C:12](=[N:13][CH:14]=[C:15]([CH3:18])[CH:16]=2)[C:11](=[O:19])[C:10]([C:20]([O:22]CC)=[O:21])=[CH:9]1.O.[OH-].[Li+]>CO.O.C(#N)C>[C:1]1([C:25]2[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=2)[CH:6]=[CH:5][CH:4]=[CH:3][C:2]=1[CH2:7][N:8]1[C:17]2[C:12](=[N:13][CH:14]=[C:15]([CH3:18])[CH:16]=2)[C:11](=[O:19])[C:10]([C:20]([OH:22])=[O:21])=[CH:9]1

Participants

6

Reactant 2

HCID 168937Lithium hydroxide, monohydrateHCID 90272040HCID 90272040, compound

Product 1

HCID 90272154HCID 90272154, compoundYield 20.2%

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 962WaterSolvent2×HCID 6342AcetonitrileSolvent

Procedure

To a solution of ethyl 1-(biphenyl-2-ylmethyl)-7-methyl-4-oxo-1,4-dihydro-1,5-naphthyridine-3-carboxylate (20) (80 mg, 0.2 mmol) in methanol (10 mL) was added the solid lithium hydroxide monohydrate (168 mg, 4.02 mmol) at room temperature under nitrogen atmosphere. It gave a clear solution within 30 minutes and this light yellow solution was stirred for 15 h at which time LCMS analysis indicated the absence of starting material. Then, it was diluted with water and the methanol was removed under vacuum. The basic aqueous layer was diluted with water and then extracted with ethyl acetate (50 mL) to remove any neutral impurities. Then, the basic aqueous layer was neutralized with 1.0N HCl. Then, the acid was extracted with ethyl acetate (2×30 mL) and the combined extracts were washed with brine solution and dried over anhydrous MgSO4. Filtration and concentration gave the yellow solids which were dissolved in acetonitrile and water. The mixture was frozen and then lyophilized under high vacuum to obtain 1-(biphenyl-2-ylmethyl)-7-methyl-4-oxo-1,4-dihydro-1,5-naphthyridine-3-carboxylic acid (21) (15 mg, 20% yield) as a light yellow solid.

Workup

  1. customIt gave a clear solution within 30 minutes
  2. customthe methanol was removed under vacuum
  3. additionThe basic aqueous layer was diluted with water
  4. extractionextracted with ethyl acetate (50 mL)
  5. customto remove any neutral impurities
  6. extractionThen, the acid was extracted with ethyl acetate (2×30 mL)
  7. washthe combined extracts were washed with brine solution
  8. dry with materialdried over anhydrous MgSO4
  9. filtrationFiltration and concentration
  10. customgave the yellow solids which
  11. temperatureThe mixture was frozen

Sources & evidence

ORD record
ord-fec669301b7346a3b673c9082dbdd0a2
Source dataset
uspto-grants-2015_12
Patent number
US09199987B2

Reaction notes

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