Methanol → Ethyl 2-methoxyquinoline-7-carboxylate

HRID 711071Notes

Reaction equation

HRID 711071 reaction equation
[CH2:1]([O:3][C:4]([C:6]1[CH:15]=[C:14]2[C:9]([CH:10]=[CH:11][CH:12]=[N+:13]2[O-])=[CH:8][CH:7]=1)=[O:5])[CH3:2].C1(C)C=CC(S(Cl)(=O)=O)=CC=1.C(N(CC)CC)C.[CH3:35][OH:36]>>[CH3:35][O:36][C:12]1[CH:11]=[CH:10][C:9]2[C:14](=[CH:15][C:6]([C:4]([O:3][CH2:1][CH3:2])=[O:5])=[CH:7][CH:8]=2)[N:13]=1

Participants

5

Reactant 4

HCID 887MethanolHCID 73974-Toluenesulfonyl chlorideHCID 8471Triethylamine2×HCID 674915557-(Ethoxycarbonyl)quinoline 1-oxide

Product 1

HCID 67491407Ethyl 2-methoxyquinoline-7-carboxylateYield 81%

Procedure

To a 0° C. solution of 7-(ethoxycarbonyl)quinoline 1-oxide (150 mg, 0.69 mmol) and toluene-4-sulphonyl chloride (171 mg, 0.89 mmol) in methanol (5 mL) was added triethylamine (0.19 mL, 1.4 mmol). The reaction was stirred at room temperature overnight. LCMS showed the reaction was incomplete. Additional triethylamine (0.05 mL) was added and the reaction was stirred for another 4 hours. The reaction was concentrated and the residue partitioned between ethyl acetate and saturated aqueous sodium carbonate. The layers were separated and the aqueous was extracted two more times with ethyl acetate. The combined organics were washed with brine, dried over sodium sulfate, filtered, and concentrated. Purification by flash column chromatography (0-40% ethyl acetate/heptanes) gave the title compound (130 mg, 81%) as a pale yellow solid. +ESI (M+H) 232.2; 1H NMR (400 MHz, CDCl3, δ): 8.49-8.60 (m, 1H), 7.95-8.05 (m, 2H), 7.75 (d, J=8.19 Hz, 1H), 6.98 (d, J=8.78 Hz, 1H), 4.43 (q, J=7.22 Hz, 2H), 4.08 (s, 3H), 1.43 (t, J=7.12 Hz, 3H).

Workup

  1. stirringthe reaction was stirred for another 4 hours
  2. concentrationThe reaction was concentrated
  3. customthe residue partitioned between ethyl acetate and saturated aqueous sodium carbonate
  4. customThe layers were separated
  5. extractionthe aqueous was extracted two more times with ethyl acetate
  6. washThe combined organics were washed with brine
  7. dry with materialdried over sodium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customPurification by flash column chromatography (0-40% ethyl acetate/heptanes)

Sources & evidence

ORD record
ord-cd9fabc726c24ae7a8d602cc495d9ef6
Source dataset
uspto-grants-2015_11
Patent number
US09181252B2

Reaction notes

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