Methanol → 4-[(1-Cyclohexylmethyl-5-hydroxy-2-oxo-3-phenyl-1,2-dihydro-[1,7]naphthyridine-6-carbonyl)-amino]-butyric acid

HRID 1411010Notes

Reaction equation

HRID 1411010 reaction equation
C([O:3][C:4](=[O:36])[CH2:5][CH2:6][CH2:7][NH:8][C:9]([C:11]1[C:12]([OH:35])=[C:13]2[C:18](=[CH:19][N:20]=1)[N:17]([CH2:21][CH:22]1[CH2:27][CH2:26][CH2:25][CH2:24][CH2:23]1)[C:16](=[O:28])[C:15]([C:29]1[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=1)=[CH:14]2)=[O:10])C.[OH-].[Na+].CO.C1COCC1>C([O-])(O)=O.[Na+]>[CH:22]1([CH2:21][N:17]2[C:18]3[C:13](=[C:12]([OH:35])[C:11]([C:9]([NH:8][CH2:7][CH2:6][CH2:5][C:4]([OH:36])=[O:3])=[O:10])=[N:20][CH:19]=3)[CH:14]=[C:15]([C:29]3[CH:30]=[CH:31][CH:32]=[CH:33][CH:34]=3)[C:16]2=[O:28])[CH2:23][CH2:24][CH2:25][CH2:26][CH2:27]1

Participants

6

Reactant 4

HCID 887MethanolHCID 8028TetrahydrofuranHCID 14798Sodium HydroxideHCID 682972714-[(1-Cyclohexylmethyl-5-hydroxy-2-oxo-3-phenyl-1,2-dihydro-[1,7]naphthyridine-6-carbonyl)-amino]-butyric acid ethyl ester

Product 1

HCID 682974634-[(1-Cyclohexylmethyl-5-hydroxy-2-oxo-3-phenyl-1,2-dihydro-[1,7]naphthyridine-6-carbonyl)-amino]-butyric acidYield 49.2%

Reagents, catalysts & solvents 1

HCID 516892Sodium BicarbonateSolvent

Procedure

A mixture of 4-[(1-cyclohexylmethyl-5-hydroxy-2-oxo-3-phenyl-1,2-dihydro-[1,7]naphthyridine-6-carbonyl)-amino]-butyric acid ethyl ester (39 mg, 0.079 mmol), 2 M NaOH (3 mL), MeOH (3 mL) and THF (3 mL) was stirred at r.t. for 16 h, then concentrated to approximately one-third of its original volume. 1 M HCl was added to acidify the mixture, and the resulting suspension was extracted with EtOAc. The organic layer was dried over MgSO4 and concentrated. The crude product was purified by silica gel chromatography (5-60% EtOAc/hexanes+1% AcOH). The product isolated was dissolved in saturated NaHCO3 and washed several times with ether. The aqueous layer was acidified to pH about 3 with 6 M HCl, and the resulting precipitate was isolated by filtration to give 18 mg of the title compound. MS: (+) m/z 464.41 (M+1).

Workup

  1. concentrationconcentrated to approximately one-third of its original volume
  2. addition1 M HCl was added
  3. extractionthe resulting suspension was extracted with EtOAc
  4. dry with materialThe organic layer was dried over MgSO4
  5. concentrationconcentrated
  6. customThe crude product was purified by silica gel chromatography (5-60% EtOAc/hexanes+1% AcOH)
  7. customThe product isolated
  8. washwashed several times with ether
  9. customthe resulting precipitate was isolated by filtration

Sources & evidence

ORD record
ord-5118e10fef2b499aa50e07561c76f47f
Source dataset
uspto-grants-2014_12
Patent number
US08921389B2

Reaction notes

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