Phosphorus oxide (P4O10) → 4-Chloro-5-fluoro-8-methoxy-2-methyl-quinoline

HRID 1959548Notes

Reaction equation

HRID 1959548 reaction equation
O=P(Cl)(Cl)[Cl:3].[F:6][C:7]1[CH:16]=[CH:15][C:14]([O:17][CH3:18])=[C:13]2[C:8]=1[C:9](O)=[CH:10][C:11]([CH3:19])=[N:12]2.O=P12OP3(OP(OP(O3)(O1)=O)(=O)O2)=O>>[Cl:3][C:9]1[C:8]2[C:13](=[C:14]([O:17][CH3:18])[CH:15]=[CH:16][C:7]=2[F:6])[N:12]=[C:11]([CH3:19])[CH:10]=1

Participants

4

Reactant 3

HCID 14812Phosphorus oxide (P4O10)HCID 24813Phosphorus oxychlorideHCID 178491787HCID 178491787, compound

Product 1

HCID 684232214-Chloro-5-fluoro-8-methoxy-2-methyl-quinoline

Conditions

Temperature
118 °C

Procedure

POCl3 (3.4 mL, 36 mmol) was added dropwise to 5-fluoro-8-methoxy-2-methyl-quinolin-4-ol (0.56 g, 2.7 mmol) at 0° C. The reaction vessel was equipped with a drying tube containing P4O10 and heated to 118° C. for 2 h. The reaction mixture was concentrated in vacuo and partitioned between DCM (30 mL), water (2 mL), and concentrated aqueous NH3 (2 mL). The organic layer was dried over Na2SO4, filtered, and concentrated in vacuo. The residue was purified by flash chromatography on silica gel (elution with EA/DCM 1:15) to give the title compound. MS (m/z): 226.5 [M+H+]

Workup

  1. customThe reaction vessel was equipped with a drying tube
  2. concentrationThe reaction mixture was concentrated in vacuo
  3. custompartitioned between DCM (30 mL), water (2 mL), and concentrated aqueous NH3 (2 mL)
  4. dry with materialThe organic layer was dried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customThe residue was purified by flash chromatography on silica gel (elution with EA/DCM 1:15)

Sources & evidence

ORD record
ord-9a3be42b1baf458fa46a03c8913195f0
Source dataset
uspto-grants-2013_04
Patent number
US08410134B2

Reaction notes

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