Water → HCID 22504141, compound

HRID 1814284Notes

Reaction equation

HRID 1814284 reaction equation
[CH3:1][C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[N:5]=[CH:4][CH:3]=1.[CH2:12]1[CH2:16][O:15][CH2:14]C1.C([N-]C(C)C)(C)C.[Li+].Cl[C:26]([O:28][CH2:29][CH3:30])=[O:27].[OH2:31]>>[CH2:29]([O:28][C:26]([CH:1]([C:14]([O:15][CH2:16][CH3:12])=[O:31])[C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[N:5]=[CH:4][CH:3]=1)=[O:27])[CH3:30]

Participants

6

Reactant 5

HCID 962WaterHCID 8028Tetrahydrofuran2×HCID 102854-MethylquinolineHCID 10928Ethyl chloroformateHCID 2724682Lithium diisopropylamide

Product 1

HCID 22504141HCID 22504141, compoundYield 60%

Conditions

Temperature
0 °C

Procedure

4-Methylquinoline (4.62 mL, 35.0 mmol) was mixed with freshly distilled THF (17 mL) in an argon-purged, round-bottom flask and was chilled to 0° C. Lithium diisopropyl amide (19.25 mL of 2.0M solution in diethyl ether, 38.5 mmol) was added via syringe. The reaction was stirred for ten minutes at 0° C. and then was cooled to −78° C. The chilled anion solution was cannula transferred to a −78° C. solution of ethyl chloroformate (10.0 mL, 105 mmol) in freshly distilled THF (17 mL) in an argon-purged, round-bottom flask. The reaction was stirred at −78° C. for fifteen minutes and then was quenched with saturated aqueous NH4Cl (5 mL). The quenched reaction was allowed to warm to room temperature. The mixture was diluted with H2O and was extracted three times with EtOAc. The organic extracts were combined, washed with brine solution, dried over Na2SO4, filtered through celite, and concentrated. Purification by flash chromatography (SiO2, 20% EtOAc-hexane) gave 4-(bis-ethoxycarbonyl methyl)-quinoline (6.02 g, 21.0 mmol) in 60% yield. MS (APCI) m/z 288.1 (M+H). 1H NMR (300 MHz) CDCl3 8.46 (d, J=8.7 Hz, 1H), 7.86 (d, J=8.1 Hz, 1H), 7.65 (m, 2H), 7.46 (m, 1H), 7.28 (m, 1H), 5.97 (s, 1H), 4.42 (q, J=7.1 Hz, 2H), 4.21 (q, J=7.1 Hz), 1.42 (t, J=7.1 Hz, 3H), 1.32 (t, J=7.2 Hz, 3H).

Workup

  1. custompurged
  2. temperaturewas cooled to −78° C
  3. customtransferred to a −78° C.
  4. custompurged
  5. stirringThe reaction was stirred at −78° C. for fifteen minutes
  6. customwas quenched with saturated aqueous NH4Cl (5 mL)
  7. customThe quenched reaction
  8. temperatureto warm to room temperature
  9. extractionwas extracted three times with EtOAc
  10. washwashed with brine solution
  11. dry with materialdried over Na2SO4
  12. filtrationfiltered through celite
  13. concentrationconcentrated
  14. customPurification by flash chromatography (SiO2, 20% EtOAc-hexane)

Sources & evidence

ORD record
ord-1f8ef389e5124f969c97c151862a96c8
Source dataset
uspto-grants-2005_04
Patent number
US06875765B2

Reaction notes

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