Potassium Carbonate → HCID 178494373, compound

HRID 469707Notes

Reaction equation

HRID 469707 reaction equation
[OH:1][C:2]1[C:11]([C:12]([OH:14])=O)=[CH:10][C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[N:3]=1.S(Cl)(Cl)=O.[NH2:19][C:20]1[C:26]([O:29][CH3:30])([O:27][CH3:28])[CH:25]2[CH:23]([O:24]2)[C:22](=[O:31])[CH:21]=1.CC(C)([O-])C.[Li+].C(=O)([O-])[O-].[K+].[K+]>O1CCCC1.C(OCC)(=O)C.CO.O>[CH3:28][O:27][C:26]1([O:29][CH3:30])[C:20]([NH:19][C:12]([C:11]2[C:2]([OH:1])=[N:3][C:4]3[C:9]([CH:10]=2)=[CH:8][CH:7]=[CH:6][CH:5]=3)=[O:14])=[CH:21][C:22](=[O:31])[CH:23]2[CH:25]1[O:24]2

Participants

9

Reactant 5

HCID 11430Potassium CarbonateHCID 24386Thionyl Chloride2×HCID 10856182HCID 10856182, compoundHCID 236647642-Propanol, 2-methyl-, lithium salt (1:1)HCID 178524031HCID 178524031, compound

Product 1

HCID 178494373HCID 178494373, compoundYield 64.7%

Reagents, catalysts & solvents 3

HCID 8028TetrahydrofuranSolvent2×HCID 8857Ethyl AcetateSolvent2×HCID 22242641Methanol--water (1/1)Solvent

Conditions

Temperature
-78 °C

Procedure

In a dry round bottom flask charged with 2-hydroxyquinoline-3-carboxylic acid (528 mg, 2.8 mmol) was added thionyl chloride (4 mL, 57 mmol). The mixture was then heated to reflux for 20 minutes before rotary evaporation of the thionyl chloride. In a separate flask amine 5 (430 mg, 2.3 mmol) was dissolved in anhydrous tetrahydrofuran (17 mL) and cooled to −78° C. under an inert nitrogen atmosphere. To the cooled amine solution was slowly added lithium tert-butoxide (in 1 M tetrahydrofuran; 3 mL, 3 mmol) followed by stirring for 15 minutes. The acid chloride was then suspended in tetrahydrofuran (12 mL) and directly added to the cooled amine solution. The reaction mixture was stirred overnight, during which time it came to room temperature. The reaction was then diluted with ethyl acetate, washed with brine, dried over anhydrous magnesium sulfate, filtered and concentrated to afford 550 mg crude material that contained 10% of the O-aroylated product (as determined by LC-MS). The solid was stirred in 8/1 methanol/water (9 mL) containing 25 mg potassium carbonate for an hour after which it was diluted with ethyl acetate and washed with saturated sodium bicarbonate solution, and brine. The ethyl acetate was dried over anhydrous magnesium sulfate, filtered and concentrated give a solid containing a small amount of the ester. The product was then purified over a small plug of silica, eluting with 95/5 dichloromethane/ethyl acetate to give 530 mg of a pale yellow solid (64% yield). The product structure was confirmed by 1H NMR. NMR (CDCl3): δ12.30 (br.s, 1H), 10.60 (br.s, 1H), 9.00 (m, 1H), 7.80 (m, 1H), 7.65 (m, 1H), 7.40 (m, 2H), 5.60 (m, 1H), 3.85 (m, 1H), 3.70 (s, 3H), 3.50 (m, 1H), 3.40 (s, 3H) ppm.

Workup

  1. temperatureThe mixture was then heated
  2. stirringThe reaction mixture was stirred overnight, during which time it
  3. customcame to room temperature
  4. washwashed with brine
  5. dry with materialdried over anhydrous magnesium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customto afford 550 mg crude material that
  9. washwashed with saturated sodium bicarbonate solution, and brine
  10. dry with materialThe ethyl acetate was dried over anhydrous magnesium sulfate
  11. filtrationfiltered
  12. concentrationconcentrated
  13. customgive a solid
  14. customThe product was then purified over a small plug of silica
  15. washeluting with 95/5 dichloromethane/ethyl acetate

Sources & evidence

ORD record
ord-98c6016bb1a34665a9fd3d445628e7bf
Source dataset
uspto-grants-2014_01
Patent number
US08629164B2

Reaction notes

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