Methyl quinoline-6-carboxylate → Methyl 2-tert-butylquinoline-6-carboxylate

HRID 1094649Notes

Reaction equation

HRID 1094649 reaction equation
[N:1]1[C:10]2[C:5](=[CH:6][C:7]([C:11]([O:13][CH3:14])=[O:12])=[CH:8][CH:9]=2)[CH:4]=[CH:3][CH:2]=1.[C:15]([Mg]Cl)([CH3:18])([CH3:17])[CH3:16]>C1COCC1.[O-2].[O-2].[Mn+4]>[C:15]([C:2]1[CH:3]=[CH:4][C:5]2[C:10](=[CH:9][CH:8]=[C:7]([C:11]([O:13][CH3:14])=[O:12])[CH:6]=2)[N:1]=1)([CH3:18])([CH3:17])[CH3:16]

Participants

5

Reactant 2

HCID 736812Methyl quinoline-6-carboxylateHCID 178418310HCID 178418310, compound

Product 1

HCID 57458162Methyl 2-tert-butylquinoline-6-carboxylateYield 27%

Reagents, catalysts & solvents 2

HCID 178418406HCID 178418406, compoundCatalystHCID 8028TetrahydrofuranSolvent3×

Conditions

Temperature
-40 °C

Procedure

To a THF (20 ml) solution of methyl quinoline-6-carboxylate (984 mg, 5.26 mmol, J. O. C., 2002, 67, 7890) was added t-butylmagnesium chloride in THF (15.8 ml, 1M solution) dropwise at −78° C. over 30 min. The mixture was stirred at −78° C. for 30 minutes and at −40° C. for 30 minutes, then at room temperature for 1 hour. The reaction was quenched with saturated ammonium chloride aqueous solution (100 ml) and extracted with EtOAc (100 ml×2) which was dried over sodium sulfate. Then, filtration, evaporation gave yellow oil, which was solved in THF (50 ml) and manganese dioxide (1.83 g 15.8 mmol) was added there. After the mixture was stirred at room temperature for 2.5 hours, the precipitate was removed through a pad of Celite and washed with EtOAc. The filtrate was concentrated and purified through silica gel column chromatography eluting with Hexane/EtOAc (20:1) to furnish the title compound (348 mg, 27% yield) as a white solid. 1H NMR (300 MHz, CDCl3) δ ppm 1.48 (9H, s), 3.99 (3H, s), 7.59 (1H, d, J=8.8 Hz), 8.08 (1H, d, J=8.8 Hz), 8.17 (1H, d, J=8.8 Hz), 8.26 (1H, dd, J=2.2, 8.8 Hz), 8.55 (1H, d, J=2.2 Hz) MS (ESI): m/z 244 (M+H)+.

Workup

  1. waitat room temperature for 1 hour
  2. customThe reaction was quenched with saturated ammonium chloride aqueous solution (100 ml)
  3. extractionextracted with EtOAc (100 ml×2) which
  4. dry with materialwas dried over sodium sulfate
  5. filtrationThen, filtration, evaporation
  6. customgave yellow oil, which
  7. stirringAfter the mixture was stirred at room temperature for 2.5 hours
  8. customthe precipitate was removed through a pad of Celite
  9. washwashed with EtOAc
  10. concentrationThe filtrate was concentrated
  11. custompurified through silica gel column chromatography
  12. washeluting with Hexane/EtOAc (20:1)

Sources & evidence

ORD record
ord-afbccdc6aeff4a95884c9b592d3be4ad
Source dataset
uspto-grants-2012_03
Patent number
US08134004B2

Reaction notes

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