Aluminium lithium hydride → 5-Fluoro-4-hydroxymethyl-6-methoxy-quinolin-3-ol

HRID 2273202Notes

Reaction equation

HRID 2273202 reaction equation
C[O:2][C:3]([C:5]1[C:14]2[C:9](=[CH:10][CH:11]=[C:12]([O:16][CH3:17])[C:13]=2[F:15])[N:8]=[CH:7][C:6]=1[O:18]C(=O)C)=O.[H-].[Al+3].[Li+].[H-].[H-].[H-]>O1CCCC1.[Cl-].[Na+].O.ClCCl.CO>[F:15][C:13]1[C:12]([O:16][CH3:17])=[CH:11][CH:10]=[C:9]2[C:14]=1[C:5]([CH2:3][OH:2])=[C:6]([OH:18])[CH:7]=[N:8]2

Participants

6

Reactant 2

HCID 21226445Aluminium lithium hydrideHCID 672479353-Acetoxy-5-fluoro-6-methoxy-quinoline-4-carboxylic acid methyl ester

Product 1

HCID 672487085-Fluoro-4-hydroxymethyl-6-methoxy-quinolin-3-olYield 23%

Reagents, catalysts & solvents 3

HCID 8028TetrahydrofuranSolventHCID 21226129Dichloromethane methanolSolventHCID 57417360Sodium chloride; waterSolvent

Conditions

Temperature
0 °C

Procedure

3-Acetoxy-5-fluoro-6-methoxy-quinoline-4-carboxylic acid methyl ester (355 mg, 1.21 mmol, 1.0 eq) is added at 0° C. to a stirred suspension of lithium aluminium hydride (138 mg, 3.63 mmol, 3.0 eq) in tetrahydrofuran (5 mL). After 2 hours stirring at 0° C., brine is used to quench the reaction and the resulting mixture is extracted with ethyl acetate (3×10 mL). The combined organic layers are dried over sodium sulfate, filtered and concentrated to give a residue that is suspended in dichloromethane:methanol (10:1, v/v) and filtered to afford 5-fluoro-4-hydroxymethyl-6-methoxy-quinolin-3-ol as an off-white solid (62 mg, 23% yield).

Workup

  1. customto quench
  2. customthe reaction
  3. extractionthe resulting mixture is extracted with ethyl acetate (3×10 mL)
  4. dry with materialThe combined organic layers are dried over sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customto give a residue that
  8. filtrationv/v) and filtered

Sources & evidence

ORD record
ord-599742809c964c3eb936766aa876f225
Source dataset
uspto-grants-2015_09
Patent number
US09120822B2

Reaction notes

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