Sulfuric Acid → Methyl 6-quinolineacetate

HRID 1798912Notes

Reaction equation

HRID 1798912 reaction equation
S(=O)(=O)(O)O.[N:6]1[C:15]2[C:10](=[CH:11][C:12]([CH2:16][C:17]([OH:19])=[O:18])=[CH:13][CH:14]=2)[CH:9]=[CH:8][CH:7]=1.[OH-].[Na+].[C:22](=O)(O)[O-].[Na+]>CO>[N:6]1[C:15]2[C:10](=[CH:11][C:12]([CH2:16][C:17]([O:19][CH3:22])=[O:18])=[CH:13][CH:14]=2)[CH:9]=[CH:8][CH:7]=1

Participants

6

Reactant 4

HCID 1118Sulfuric AcidHCID 14798Sodium HydroxideHCID 516892Sodium BicarbonateHCID 117887092-(Quinolin-6-yl)acetic acid

Product 1

HCID 1514202Methyl 6-quinolineacetateYield 98%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

As shown in step i of Scheme 1, concentrated sulfuric acid (206 mL, 3.868 mol) was added dropwise to a solution of 2-(quinolin-6-yl)acetic acid (compound 1001, 658.2 g, 3.516 mol, Okeanos Tech Co., Cat. No. OK-J-05024) in 6.5 liters of methanol. During the addition, a slight exotherm was observed. After the addition was complete, the reaction was stirred at reflux for 4 hours. After cooling, the volatiles were removed under reduced pressure, the resulting residue was diluted with 4 liters of ethyl acetate, cooled in an ice bath, treated with 2N NaOH (2.1 liters, 1.2 equiv.) until a pH of 4 was achieved, and then treated with saturated sodium bicarbonate until a pH of 8 was achieved. The layers were separated and the aqueous layer extracted twice with ethyl acetate. The combined organics were washed with saturated sodium bicarbonate, washed with water, washed with brine, dried over anhydrous MgSO4, filtered, and evaporated under reduced pressure to afford methyl 2-(quinolin-6-yl)acetate as a clear brown oil (compound 1002, 696.8 g, 98% yield): ESMS (M+1), 202.14; 1H NMR (300.0 MHz, DMSO-d6) δ 8.90 (1H, dd, J=1.7, 4.2 Hz), 8.14-8.10 (1H, m), 8.08 (1H, d, J=8.7 Hz), 7.72 (1H, d, J=1.4 Hz), 7.65 (1H, dd, J=2.0, 8.7 Hz), 7.40 (1H, dd, J=4.2, 8.3 Hz), 3.83 (2H, s), 3.73 (3H, s).

Workup

  1. additionDuring the addition
  2. additionAfter the addition
  3. temperatureat reflux for 4 hours
  4. temperatureAfter cooling
  5. customthe volatiles were removed under reduced pressure
  6. additionthe resulting residue was diluted with 4 liters of ethyl acetate
  7. temperaturecooled in an ice bath
  8. customThe layers were separated
  9. extractionthe aqueous layer extracted twice with ethyl acetate
  10. washThe combined organics were washed with saturated sodium bicarbonate
  11. washwashed with water
  12. washwashed with brine
  13. dry with materialdried over anhydrous MgSO4
  14. filtrationfiltered
  15. customevaporated under reduced pressure

Sources & evidence

ORD record
ord-86521e8eedf0436cb3a3e341f1db7a1e
Source dataset
uspto-grants-2013_01
Patent number
US08343998B2

Reaction notes

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