Hydrochloric Acid → (S)-7-(2-methoxypropoxy)-2-methylquinoline

HRID 339066Notes

Reaction equation

HRID 339066 reaction equation
[CH3:1][C:2]1[CH:11]=[CH:10][C:9]2[C:4](=[CH:5][C:6]([OH:12])=[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][C@@H:34]([CH3:37])[CH2:35]O.N(C(OC(C)C)=O)=NC(OC(C)C)=O.Cl>C1COCC1.CCOC(C)=O.O>[CH3:32][O:33][C@@H:34]([CH3:37])[CH2:35][O:12][C:6]1[CH:5]=[C:4]2[C:9]([CH:10]=[CH:11][C:2]([CH3:1])=[N:3]2)=[CH:8][CH:7]=1

Participants

9

Reactant 5

HCID 313Hydrochloric AcidHCID 11776TriphenylphosphineHCID 75555Diisopropyl diazene-1,2-dicarboxylateHCID 6424022-Methoxy-1-propanol, (2S)-HCID 1354519692-Methylquinolin-7-ol

Product 1

HCID 70983167(S)-7-(2-methoxypropoxy)-2-methylquinolineYield 51%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a stirred solution of 2-methylquinolin-7-ol (1.00 g, 6.28 mmol), PPh3 (4.12 g, 15.7 mmol) and (S)-2-methoxypropan-1-ol (0.679 g, 7.54 mmol) in THF (60 mL) was added dropwise diisopropyl azodicarboxylate (2.05 mL, 10.1 mmol) at 0° C. under nitrogen. The reaction mixture was stirred at ambient temperature overnight. The reaction was then heated at 50° C. for additional 2 hours. After cooling, to the reaction were added 4N HCl (3.1 mL), water (100 mL) and EtOAc (200 mL). The aqueous layer was separated and washed with EtOAc (100 mL). The aqueous was neutralized with ammonium hydroxide to about pH 9, extracted with EtOAc, washed with brine, dried and concentrated under reduced pressure. The residue was purified by flash chromatography on silica gel (1:1 hexane/EtOAc) to give (S)-7-(2-methoxypropoxy)-2-methylquinoline (0.738 g, 51%).

Workup

  1. temperatureThe reaction was then heated at 50° C. for additional 2 hours
  2. temperatureAfter cooling, to the reaction
  3. customThe aqueous layer was separated
  4. washwashed with EtOAc (100 mL)
  5. extractionextracted with EtOAc
  6. washwashed with brine
  7. customdried
  8. concentrationconcentrated under reduced pressure
  9. customThe residue was purified by flash chromatography on silica gel (1:1 hexane/EtOAc)

Sources & evidence

ORD record
ord-ed0c4bf009384be792b830996bf2be43
Source dataset
uspto-grants-2014_11
Patent number
US08889704B2

Reaction notes

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