8-Hydroxyquinoline → CID 57672264

HRID 252066Notes

Reaction equation

HRID 252066 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([C:24]#[N:25])[CH:5]=[C:6]2[C:10]=1[C:9](=[O:11])[N:8]([CH2:12][C:13]1[CH:18]=[CH:17][C:16]([O:19][C:20]([F:23])([F:22])[F:21])=[CH:15][CH:14]=1)[CH2:7]2.OC1C=CC=C2C=1N=CC=C2.Cl.[NH2:38][OH:39].C(=O)([O-])[O-].[Na+].[Na+]>C(O)C.O>[Cl:1][C:2]1[CH:3]=[C:4]([C:24]([NH:38][OH:39])=[NH:25])[CH:5]=[C:6]2[C:10]=1[C:9](=[O:11])[N:8]([CH2:12][C:13]1[CH:18]=[CH:17][C:16]([O:19][C:20]([F:21])([F:22])[F:23])=[CH:15][CH:14]=1)[CH2:7]2

Participants

7

Reactant 4

HCID 19238-HydroxyquinolineHCID 10340Sodium CarbonateHCID 443297Hydroxyamine hydrochlorideHCID 579496207-chloro-1-oxo-2-(4-trifluoromethoxy-benzyl)-2,3-dihydro-1H-isoindole-5-carbonitrile

Product 1

HCID 178513331CID 57672264Yield 92%

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 962WaterSolvent2×

Procedure

To a suspension of 7-chloro-1-oxo-2-[4-(trifluoromethoxy)benzyl]isoindoline-5-carbonitrile (500 mg, 1.36 mmol) in ethanol (2 ml), 8-hydroxyquinoline (495 mg, 3.41 mmol) was added, followed by a solution of hydroxylamine hydrochloride (199 mg, 2.86 mmol) in water (1 ml) and a solution of sodium carbonate (230 mg, 2.2 mmol) in water (1 ml). The resulting mixture was refluxed for 4 hours. After removal of solvents, the residue was loaded to a flash chromatography. The product was purified (20% EtOAc/hexanes to 2% ammonia in MeOH/EtOAc) and obtained a 500 mg of greenish foam (90%). 1H NMR (300 MHz, CDCl3): δ 10.04 (s, 1H) 7.48-7.61 (m, 2H), 7.28-7.36 (m, 2H), 7.17-7.21 (m, 2H), 6.04 (br, 1H), 4.77 (s, 2H), 4.22 (s, 2H).

Workup

  1. additionwas added
  2. temperatureThe resulting mixture was refluxed for 4 hours
  3. customAfter removal of solvents
  4. customThe product was purified (20% EtOAc/hexanes to 2% ammonia in MeOH/EtOAc)

Sources & evidence

ORD record
ord-df52f94375d04538b7672a1486ad98c6
Source dataset
uspto-grants-2011_01
Patent number
US07868008B2

Reaction notes

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