Methanol → HCID 18698673, compound

HRID 2289954Notes

Reaction equation

HRID 2289954 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][NH:9][C:10]([C:12]2[C:21](=[O:22])[C:20]3[C:15](=[C:16]([F:25])[C:17](F)=[C:18]([F:23])[CH:19]=3)[N:14]([CH2:26][O:27][CH2:28][CH2:29][Si:30]([CH3:33])([CH3:32])[CH3:31])[CH:13]=2)=[O:11])=[CH:4][CH:3]=1.[CH3:34][OH:35].[H-].[Na+].[Cl-].[NH4+]>CN(C=O)C>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][NH:9][C:10]([C:12]2[C:21](=[O:22])[C:20]3[C:15](=[C:16]([F:25])[C:17]([O:35][CH3:34])=[C:18]([F:23])[CH:19]=3)[N:14]([CH2:26][O:27][CH2:28][CH2:29][Si:30]([CH3:33])([CH3:31])[CH3:32])[CH:13]=2)=[O:11])=[CH:4][CH:3]=1

Participants

6

Reactant 4

HCID 887MethanolHCID 24758Sodium hydrideHCID 25517Ammonium ChlorideHCID 18698511HCID 18698511, compound

Product 1

HCID 18698673HCID 18698673, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
140 °C

Procedure

N-((4-Chlorophenyl)methyl)-4-oxo-6,7,8-trifluoro-1-(2-(trimethylsilyl)ethoxy) methyl-3-quinolinecarboxamide (1.00 g) from Preparation No. 13 and methanol (163 μL) are dissolved in DMF (20 mL). Sodium hydride (60% dispersion, 80 mg) is added and the mixture is heated to 140° C. for 1 h. The mixture is allowed to cool to rt, is poured into sat. aq. ammonium chloride (100 mL), and is extracted with ethyl acetate (3×50 mL). The organic layer is washed with brine (10 mL), dried (MgSO4), and concentrated. The crude product is purified by column chromatography (heptane/ethyl acetate, 4/1; 3/1) to afford N-((4-chlorophenyl)methyl)-6,8-difluoro-7-methoxy-4-oxo-1-(2-(trimethylsilyl)ethoxy)methyl-3-quinolinecarboxamide. The resulting crude amide is suspended in ethanol (15 mL), heated to 85° C., and to the mixture is added 50% aq. hydrochloric acid (5 mL). The mixture is heated an additional 1.5 h and allowed to cool to rt. The reaction mixture is neutralized with solid sodium bicarbonate and filtered. The solids are washed with ethanol (10 mL) followed by ethyl acetate (20 mL), and the combined filtrates are concentrated to afford a tan solid. The crude product is purified by recrystallization from acetic acid/water followed by column chromatography (heptane/2-propanol, 95/5) to afford 27 mg of the title compound.

Workup

  1. temperatureto cool to rt
  2. extractionis extracted with ethyl acetate (3×50 mL)
  3. washThe organic layer is washed with brine (10 mL)
  4. dry with materialdried (MgSO4)
  5. concentrationconcentrated
  6. customThe crude product is purified by column chromatography (heptane/ethyl acetate, 4/1; 3/1)

Sources & evidence

ORD record
ord-2bfae1161b974a5e821687a17f5ea4dd
Source dataset
uspto-grants-2000_07
Patent number
US06093732

Reaction notes

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