Methanol → HCID 67057975, compound

HRID 886772Notes

Reaction equation

HRID 886772 reaction equation
[CH3:1][O:2][Na].CO.Br[C:7]1[C:16]([OH:17])=[C:15]2[C:10]([CH:11]=[CH:12][C:13]([CH3:18])=[N:14]2)=[CH:9][CH:8]=1.C(N(CC([O-])=O)CC(O)=O)CN(CC([O-])=O)CC(O)=O.[Na+].[Na+].C([O-])(O)=O.[Na+]>CN(C=O)C.C(O)(=O)C.O>[CH3:18][C:13]1[CH:12]=[CH:11][C:10]2[C:15](=[C:16]([OH:17])[C:7]([O:2][CH3:1])=[CH:8][CH:9]=2)[N:14]=1

Participants

9

Reactant 5

HCID 887MethanolHCID 8759EDTA disodium saltHCID 516892Sodium BicarbonateHCID 21824657HCID 21824657, compoundHCID 178418582HCID 178418582, compound

Product 1

HCID 67057975HCID 67057975, compoundYield 60%

Reagents, catalysts & solvents 3

HCID 176Acetic AcidSolventHCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

The protocol was established using works by: D. Planchenault et al. Tetrahedron 1995, 51, 5823-5830. A solution of CH3ONa (30% by weight) in CH3OH (8.04 ml; 42.2 mmol) is added to a solution of 7-bromo-2-methyl-8-hydroxyquinoline (1.00 g; 4.22 mmol) in DMF (60 ml). The mixture is stirred for 10 minutes under argon. CuCl2.2H2O (0.22 g; 1.27 mmol) is added and the reaction mixture is heated under reflux for 30 hours. After cooling, water (50 ml) and disodium EDTA dihydrate (10 g; 27 mmol) are added and the medium is stirred for 1 hour. The solution is lightly acidified with acetic acid (3 ml, pH=4-5) and subsequently rebasified gently with a saturated aqueous solution of NaHCO3 (3 ml). The aqueous phase is extracted with CH2Cl2 (3×100 ml). The combined organic phases are dried over anhydrous Na2SO4 and concentrated under reduced pressure. The solid obtained is purified by silica gel chromatography, eluted using a gradient of CH2Cl2/CH3OH/CH3COOH (94/4/2, v/v) to CH2Cl2/CH3OH/CH3COOH (94/5/1, v/v) then to CH2Cl2/CH3OH (94/6, v/v). Fractions containing the product are combined and washed with a saturated aqueous solution of NaHCO3 (3×100 ml). The organic phase is dried over anhydrous Na2SO4 and concentrated under reduced pressure to yield 2-methyl-7-(methyloxy)-8-quinolinol in the form of a white powder (480 mg; 2.54 mmol, yield=60%). NMR-1H (250 MHz, CDCl3) δ, ppm: 7.95 (d, 3J (H, H)=8.5 Hz, 1H); 7.26 (s, 2H); 7.15 (d, 3J (H, H)=8.5 Hz, 1H); 4.03 (s, 3H); 2.69 (s, 3H). NMR-13C (63 MHz, CDCl3) δ, ppm: 157.6 (Cq); 143.9 (Cq); 139.3 (Cq); 138.0 (Cq); 136.0 (CH); 121.7 (Cq); 120.6 (CH); 117.3 (CH); 115.2 (CH); 57.2 (CH3); 25.1 (CH3). MS (CID, NH3): m/z=190 (MH+). Analysis (%) for C11H11NO2: calculated C, 69.83. H, 5.86. N, 7.40. found C, 69.40. H, 5.85. N, 7.47.

Workup

  1. temperaturethe reaction mixture is heated
  2. temperatureunder reflux for 30 hours
  3. temperatureAfter cooling
  4. stirringthe medium is stirred for 1 hour
  5. extractionThe aqueous phase is extracted with CH2Cl2 (3×100 ml)
  6. dry with materialThe combined organic phases are dried over anhydrous Na2SO4
  7. concentrationconcentrated under reduced pressure
  8. customThe solid obtained
  9. customis purified by silica gel chromatography
  10. washeluted
  11. additionFractions containing the product
  12. washwashed with a saturated aqueous solution of NaHCO3 (3×100 ml)
  13. dry with materialThe organic phase is dried over anhydrous Na2SO4
  14. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-2e89ea28e6454094939a99af953f4b36
Source dataset
uspto-grants-2012_08
Patent number
US08247396B2

Reaction notes

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