Hydrochloric Acid → 8-(1,3-Dimethoxypropan-2-yloxy)-2-methylquinoline

HRID 339056Notes

Reaction equation

HRID 339056 reaction equation
[CH3:1][C:2]1[CH:11]=[CH:10][C:9]2[C:4](=[C:5]([OH:12])[CH:6]=[CH:7][CH:8]=2)[N:3]=1.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.[CH3:32][O:33][CH2:34][CH:35](O)[CH2:36][O:37][CH3:38].CC(OC(/N=N/C(OC(C)C)=O)=O)C.Cl>C1COCC1.C(OCC)(=O)C.O>[CH3:32][O:33][CH2:34][CH:35]([O:12][C:5]1[CH:6]=[CH:7][CH:8]=[C:9]2[C:4]=1[N:3]=[C:2]([CH3:1])[CH:11]=[CH:10]2)[CH2:36][O:37][CH3:38]

Participants

9

Reactant 5

HCID 313Hydrochloric AcidHCID 11776TriphenylphosphineHCID 121901,3-Dimethoxy-2-propanolHCID 132242-Methyl-8-hydroxyquinolineHCID 5363146Diisopropyl azodicarboxylate

Product 1

HCID 709841378-(1,3-Dimethoxypropan-2-yloxy)-2-methylquinolineYield 89.15%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of 2-methylquinolin-8-ol (4.10 g, 25.76 mmol), PPh3 (16.89 g, 64.39 mmol) and 1,3-dimethoxypropan-2-ol (4.02 g, 33.48 mmol) in THF (20 mL) was added DIAD (8.40 mL, 41.21 mmol) dropwise at ambient temperature. The reaction mixture was stirred at room temperature for two days. 4 N HCl (7.73 mL, 30.91 mmol in water), water (20 mL), and ethyl acetate (50 mL) were added. The aqueous layer was separated and washed with ethyl acetate. The aqueous layer was neutralized with ammonium hydroxide to about pH 9 and extracted with ethyl acetate (50 mL). The organic layer was separated, washed with brine, dried (sodium sulfate), filtered and concentrated under reduced pressure. The residue was purified by flash chromatography on silica gel (1:2 hexane/ethyl acetate) to give 8-(1,3-dimethoxypropan-2-yloxy)-2-methylquinoline (6.00 g, 89.15%) as an oil.

Workup

  1. customThe aqueous layer was separated
  2. washwashed with ethyl acetate
  3. extractionextracted with ethyl acetate (50 mL)
  4. customThe organic layer was separated
  5. washwashed with brine
  6. dry with materialdried (sodium sulfate)
  7. filtrationfiltered
  8. concentrationconcentrated under reduced pressure
  9. customThe residue was purified by flash chromatography on silica gel (1:2 hexane/ethyl acetate)

Sources & evidence

ORD record
ord-d2d57cd034be462d8e17eb4ed307e329
Source dataset
uspto-grants-2014_11
Patent number
US08889704B2

Reaction notes

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