Glycerol → 7-Methoxy-6-methylquinoline

HRID 532841Notes

Reaction equation

HRID 532841 reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[C:5]([CH:7]=[CH:8][C:9]=1[CH3:10])[NH2:6].[N+]([C:14]1[CH:15]=C(S([O-])(=O)=O)C=C[CH:19]=1)([O-])=O.[Na+].S(O)(C)(=O)=O.OCC(CO)O.[OH-].[Na+]>O1CCOCC1>[CH3:10][C:9]1[CH:8]=[C:7]2[C:5](=[CH:4][C:3]=1[O:2][CH3:1])[N:6]=[CH:15][CH:14]=[CH:19]2

Participants

7

Reactant 5

HCID 753GlycerolHCID 6395Methanesulfonic AcidHCID 14798Sodium HydroxideHCID 278823-Methoxy-4-methylanilineHCID 31389Sodium 3-nitrobenzenesulfonate

Product 1

HCID 593661657-Methoxy-6-methylquinolineYield 98.2%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Conditions

Temperature
150 °C

Procedure

Using a minimal amount of dioxane, 3-methoxy-4-methylaniline (5.00 g, 36.5 mmol) was slowly added to a mixture of sodium m-nitrobenzenesulfonate (6.62 g, 29.4 mmol), MsOH (20 mL), and FeSO4.7H2O (0.39 g, 1.4 mmol) in a 100 mL round bottom flask heated to an internal temperature of 145-155° C. Glycerol (10.75 g, 116.8 mmol) was then added dropwise via addition funnel while keeping the internal temperature at 145-155° C. After addition, the reaction was stirred in a 150° C. oil bath until LCMS indicated completion (4-6 h). After being cooled to rt, ice (20 g) was added, then the solution was neutralized with 10 N NaOH (calculated to same eq of MsOH) at a speed to keep the internal temperature below 40° C. A thick suspension appeared after addition, and this was extracted with EtOAc (50 mL×3). The organic layer was filtered through a Celite pad to remove insoluble black particles and then purified by flash column chromatography on silica gel to give the desired product (5.0 g, 79%). MS (ES) m/z 174.1 (M+H+).

Workup

  1. customat 145-155° C
  2. additionAfter addition
  3. customcompletion (4-6 h)
  4. temperatureAfter being cooled to rt
  5. customthe internal temperature below 40° C
  6. additionafter addition
  7. extractionthis was extracted with EtOAc (50 mL×3)
  8. filtrationThe organic layer was filtered through a Celite pad
  9. customto remove insoluble black particles
  10. custompurified by flash column chromatography on silica gel

Sources & evidence

ORD record
ord-643705ef8a114d9d916aff19b4da72f6
Source dataset
uspto-grants-2014_10
Patent number
US08853202B2

Reaction notes

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