Hydrochloric Acid → Ethyl 1-cyclopropyl-6,7-difluoro-1,2,3,4-tetrahydro-8-methoxy-5-nitro-4-oxo-2-phenylquinoline-3-carboxylate

HRID 561151Notes

Reaction equation

HRID 561151 reaction equation
[CH:1]1([N:4]2[C:13]3[C:8](=[C:9]([N+:18]([O-:20])=[O:19])[C:10]([F:17])=[C:11]([F:16])[C:12]=3[O:14][CH3:15])[C:7](=[O:21])[C:6]([C:22]([O:24][CH2:25][CH3:26])=[O:23])=[CH:5]2)[CH2:3][CH2:2]1.Cl>C1COCC1.C1([Mg]Br)C=CC=CC=1>[CH:1]1([N:4]2[C:13]3[C:8](=[C:9]([N+:18]([O-:20])=[O:19])[C:10]([F:17])=[C:11]([F:16])[C:12]=3[O:14][CH3:15])[C:7](=[O:21])[CH:6]([C:22]([O:24][CH2:25][CH3:26])=[O:23])[CH:5]2[C:8]2[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=2)[CH2:2][CH2:3]1

Participants

5

Reactant 2

HCID 313Hydrochloric AcidHCID 10666701Ethyl 1-cyclopropyl-6,7-difluoro-1,4-dihydro-8-methoxy-5-nitro-4-oxoquinoline-3-carboxylate

Product 1

HCID 66999747Ethyl 1-cyclopropyl-6,7-difluoro-1,2,3,4-tetrahydro-8-methoxy-5-nitro-4-oxo-2-phenylquinoline-3-carboxylateYield 169.9%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent2×HCID 178418255HCID 178418255, compoundSolvent

Conditions

Temperature
-78 °C

Procedure

To a stirred solution of ethyl 1-cyclopropyl-6,7-difluoro-1,4-dihydro-8-methoxy-5-nitro-4-oxoquinoline-3-carboxylate (3.00 g, 8.15 mmol) and cuprous iodide (467 mg, 2.45 mmol) in THF (80 mL), 2 M phenylmagnesium bromide in THF (6.10 mL, 12.2 mmol) was added under argon atmosphere at −78° C. After stirred at −78° C. for 1 h and at room temperature for 2 h, the reaction mixture was poured into ice-water (400 mL) and concentrated HCl (40 mL) was added to stirred for 30 min. The crude product was extracted with EtOAc, washed with saturated aq. NaHCO3 and brine, dried over MgSO4 and the solvent was removed in vacuo. The crude product was purified by column chromatography (Hexane:EtOAc 40:1→10:1) to yield ethyl 1-cyclopropyl-6,7-difluoro-1,2,3,4-tetrahydro-8-methoxy-5-nitro-4-oxo-2-phenylquinoline-3-carboxylate (3.09 g, 85%) as a yellow solid.

Workup

  1. additionwas added
  2. stirringto stirred for 30 min
  3. extractionThe crude product was extracted with EtOAc
  4. washwashed with saturated aq. NaHCO3 and brine
  5. dry with materialdried over MgSO4
  6. customthe solvent was removed in vacuo
  7. customThe crude product was purified by column chromatography (Hexane:EtOAc 40:1→10:1)

Sources & evidence

ORD record
ord-88fb22268caa4d77868ca17d54f49a73
Source dataset
uspto-grants-2011_11
Patent number
US08063221B2

Reaction notes

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