Ammonium Chloride → (5-Fluoro-pyridin-2-yl)-(8-nitro-quinolin-7-yl)-methanol

HRID 513657Notes

Reaction equation

HRID 513657 reaction equation
[Li]CCCC.Br[C:7]1[CH:12]=[CH:11][C:10]([F:13])=[CH:9][N:8]=1.[N+:14]([C:17]1[C:18]([CH:27]=[O:28])=[CH:19][CH:20]=[C:21]2[C:26]=1[N:25]=[CH:24][CH:23]=[CH:22]2)([O-:16])=[O:15].[NH4+].[Cl-]>C1(C)C=CC=CC=1.C1COCC1>[F:13][C:10]1[CH:11]=[CH:12][C:7]([CH:27]([C:18]2[C:17]([N+:14]([O-:16])=[O:15])=[C:26]3[C:21]([CH:22]=[CH:23][CH:24]=[N:25]3)=[CH:20][CH:19]=2)[OH:28])=[N:8][CH:9]=1

Participants

7

Reactant 4

HCID 25517Ammonium ChlorideHCID 27831712-Bromo-5-fluoropyridineHCID 117695548-Nitro-7-quinolinecarboxaldehyde2×HCID 178418339Butyllithium

Product 1

HCID 68183128(5-Fluoro-pyridin-2-yl)-(8-nitro-quinolin-7-yl)-methanolYield 46.8%

Reagents, catalysts & solvents 2

HCID 1140TolueneSolvent2×HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-78 °C

Procedure

n-BuLi (1.6M in hexane; 5.5 ml, 8.9 mmol) was added to anhydrous toluene (35 ml) at −78° C. under an N2 atmosphere followed by dropwise addition of a solution 2-bromo-5-fluoropyridine (1.56 g, 8.9 mmol) in anhydrous toluene (10 ml). The mixture was stirred at −78° C. for 45 min. The mixture was added to a solution of 8-nitroquinoline-7-carbaldehyde (Intermediate 204) (1 g, 5.0 mmol) in THF (50 ml) at −78° C. over 10 min. The mixture was stirred at −78° C. for a further 1 h. NH4Cl solution (10 ml) was added at −78° C. and the mixture was warmed to room temperature. The solvent was removed in vacuo. The residue was dissolved in DCM (50 ml) and the organic phase was washed with sat. NaHCO3 solution, dried (Na2SO4) and concentrated in vacuo. The crude residue was purified by column chromatography DCM/MeOH (99:1) as the eluent to give the title compound (700 mg, 46%).

Workup

  1. stirringThe mixture was stirred at −78° C. for a further 1 h
  2. temperaturethe mixture was warmed to room temperature
  3. customThe solvent was removed in vacuo
  4. dissolutionThe residue was dissolved in DCM (50 ml)
  5. washthe organic phase was washed with sat. NaHCO3 solution
  6. dry with materialdried (Na2SO4)
  7. concentrationconcentrated in vacuo
  8. customThe crude residue was purified by column chromatography DCM/MeOH (99:1) as the eluent

Sources & evidence

ORD record
ord-fb12663e2dcc43fdb5d060f2b6dccc0d
Source dataset
uspto-grants-2015_08
Patent number
US09102688B2

Reaction notes

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