Diisopropylamine → Ethyl 8-nitro-4-oxo-2-(3-(trifluoromethyl)phenyl)-1,4-dihydroquinoline-3-carboxylate

HRID 520459Notes

Reaction equation

HRID 520459 reaction equation
C(NC(C)C)(C)C.[Li]CCCC.[C:13]([O:16][CH2:17][CH3:18])(=[O:15])[CH3:14].[N+:19]([C:22]1[C:27]2[N:28]=[C:29]([C:33]3[CH:38]=[CH:37][CH:36]=[C:35]([C:39]([F:42])([F:41])[F:40])[CH:34]=3)[O:30][C:31](=O)[C:26]=2[CH:25]=[CH:24][CH:23]=1)([O-:21])=[O:20].[Li+].CC([N-]C(C)C)C.CCOC(C)=O.[OH-].[Na+]>C1COCC1.[Cl-].[Na+].O>[N+:19]([C:22]1[CH:23]=[CH:24][CH:25]=[C:26]2[C:27]=1[NH:28][C:29]([C:33]1[CH:38]=[CH:37][CH:36]=[C:35]([C:39]([F:40])([F:41])[F:42])[CH:34]=1)=[C:14]([C:13]([O:16][CH2:17][CH3:18])=[O:15])[C:31]2=[O:30])([O-:21])=[O:20]

Participants

9

Reactant 6

HCID 7912DiisopropylamineHCID 8857Ethyl AcetateHCID 14798Sodium HydroxideHCID 585528458-nitro-2-(3-(trifluoromethyl)phenyl)-4H-benzo[d][1,3]oxazin-4-oneHCID 86660235LDA EtOAcHCID 178418339Butyllithium

Product 1

HCID 58552877Ethyl 8-nitro-4-oxo-2-(3-(trifluoromethyl)phenyl)-1,4-dihydroquinoline-3-carboxylateYield 42%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent2×HCID 57417360Sodium chloride; waterSolvent

Conditions

Temperature
-78 °C

Procedure

A solution of diisopropylamine (7.00 mL, 50.0 mmol) in THF (100 mL) was cooled to −78° C., and n-BuLi (20.0 mL, 2.5 M in hexanes, 50.0 mmol) was added. After stirring for 20 min at −78° C., ethyl acetate (5.72 mL, 58.6 mmol) was added. The solution was stirred at −78° C. for 10 min, warmed to 0° C. and stirred for 10 min, then cooled back to −78° C. A solution of 8-nitro-2-(3-(trifluoromethyl)phenyl)-4H-benzo[d][1,3]oxazin-4-one 3 (9.85 g, 29.3 mmol) in THF (100 mL) was added over 5 min to the LDA/EtOAc mixture. The reaction was stirred at −78° C. for 1 h, then warmed to room temperature over 2 h. 1N NaOH (50 mL) was then added, and the reaction stirred vigorously overnight. Brine (50 mL) was added, and the organic layer separated. The aqueous layer was extracted with ethyl acetate (2×100 mL), and the combined organic layers dried with MgSO4 and concentrated under reduced pressure. The remaining material was purified by MPLC (using a gradient of 20% to 50% EtOAc in pentane) to give 36 (5.00 g, 42% yield).

Workup

  1. stirringThe solution was stirred at −78° C. for 10 min
  2. temperaturewarmed to 0° C.
  3. stirringstirred for 10 min
  4. temperaturecooled back to −78° C
  5. stirringThe reaction was stirred at −78° C. for 1 h
  6. temperaturewarmed to room temperature over 2 h
  7. stirringthe reaction stirred vigorously overnight
  8. customthe organic layer separated
  9. extractionThe aqueous layer was extracted with ethyl acetate (2×100 mL)
  10. dry with materialthe combined organic layers dried with MgSO4
  11. concentrationconcentrated under reduced pressure
  12. customThe remaining material was purified by MPLC (

Sources & evidence

ORD record
ord-6644696c027542ec97b0f176c4d34f3b
Source dataset
uspto-grants-2016_05
Patent number
US09326986B2

Reaction notes

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