Sodium Hydroxide → Methyl 7-bromoquinoline-4-carboxylate

HRID 2423400Notes

Reaction equation

HRID 2423400 reaction equation
[Br:1][C:2]1[CH:11]=[C:10]2[C:5]([C:6]([C:16]([O:18][CH3:19])=[O:17])=[CH:7][C:8](C(OC)=O)=[N:9]2)=[CH:4][CH:3]=1.[OH-].[Na+].S(Cl)(Cl)=O>CCO.O.C1COCC1>[Br:1][C:2]1[CH:11]=[C:10]2[C:5]([C:6]([C:16]([O:18][CH3:19])=[O:17])=[CH:7][CH:8]=[N:9]2)=[CH:4][CH:3]=1

Participants

7

Reactant 3

HCID 14798Sodium HydroxideHCID 24386Thionyl Chloride2×HCID 67245888Dimethyl 7-bromoquinoline-2,4-dicarboxylate

Product 1

HCID 53419781Methyl 7-bromoquinoline-4-carboxylateYield 52.1%

Reagents, catalysts & solvents 3

HCID 702EthanolSolventHCID 962WaterSolvent2×HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
50 °C

Procedure

To a solution of 750 mg (2.31 mmol) of dimethyl 7-bromo-2,4-quinolinedicarboxylate in a mixture of 20 mL of EtOH, 10 mL THF and 4 mL of H2O was added 925 mg (23.1 mmol) of NaOH. The mixture was stirred at 50° C. An additional 10 mL of THF and 15 mL of H2O were added after 5 min. After 30 min total at 50° C., the solution was concentrated to ⅓ volume and the pH was adjusted to 4.0 with 1.0 N HCl (aq) followed by the addition of 100 mL of H2O. The resulting solids were collected by suction filtration, washed with H2O and dried. The solids were then added to 10 mL of diphenyl ether and the mixture stirred at 215° C. for 20 min. Upon cooling, 20 mL of hexanes was added and the resulting solids were collected by suction filtration, washed with hexanes and dried. The solids were then suspended in 20 mL of MeOH and 505 μL (6.90 mmol) of thionyl chloride was added. The mixture was refluxed for 1 hr, then an additional 505 μL (6.90 mmol) of thionyl chloride was added. After an additional 1 hr of refluxing, the solvent was evaporated. The residue was diluted with EtOAc then washed with saturated Na2CO3 (aq) and brine then dried over Na2SO4. Concentration of the solution yielded 320 mg (52%) of methyl 7-bromo-4-quinolinecarboxylate as a beige solid. 1H NMR (400 MHz, CDCl3): δ 9.01 (d, J=4 Hz, 1H), 8.70 (d, J=9 Hz, 1H), 8.35 (s, 1H), 7.92 (d, J=4 Hz, 1H), 7.75-7.72 (m, 1H), 4.03 (s, 3H). ESI-LCMS m/z 267 (M+H)+.

Workup

  1. concentrationthe solution was concentrated
  2. additionfollowed by the addition of 100 mL of H2O
  3. filtrationThe resulting solids were collected by suction filtration
  4. washwashed with H2O
  5. customdried
  6. additionThe solids were then added to 10 mL of diphenyl ether
  7. stirringthe mixture stirred at 215° C. for 20 min
  8. temperatureUpon cooling
  9. addition20 mL of hexanes was added
  10. filtrationthe resulting solids were collected by suction filtration
  11. washwashed with hexanes
  12. customdried
  13. temperatureThe mixture was refluxed for 1 hr
  14. temperatureAfter an additional 1 hr of refluxing
  15. customthe solvent was evaporated
  16. additionThe residue was diluted with EtOAc
  17. washthen washed with saturated Na2CO3 (aq) and brine
  18. dry with materialthen dried over Na2SO4

Sources & evidence

ORD record
ord-64a91cccd239431ca736047e04148f21
Source dataset
uspto-grants-2011_06
Patent number
US07960552B2

Reaction notes

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