Sodium Azide → 3-azidomethyl-7-fluoro-1-(2-fluoro-phenyl)-1H-quinolin-4-one

HRID 1887812Notes

Reaction equation

HRID 1887812 reaction equation
[F:1][C:2]1[CH:11]=[C:10]2[C:5]([C:6](=[O:20])[C:7]([CH3:19])=[CH:8][N:9]2[C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][C:13]=2[F:18])=[CH:4][CH:3]=1.BrN1C(=O)CCC1=O.N(C(C)(CC(C)C)C#N)=NC(C)(CC(C)C)C#N.[N-:47]=[N+:48]=[N-:49].[Na+]>C(Cl)(Cl)(Cl)Cl>[N:47]([CH2:19][C:7]1[C:6](=[O:20])[C:5]2[C:10](=[CH:11][C:2]([F:1])=[CH:3][CH:4]=2)[N:9]([C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][C:13]=2[F:18])[CH:8]=1)=[N+:48]=[N-:49]

Participants

6

Reactant 4

HCID 33557Sodium AzideHCID 67184N-bromobutanimideHCID 915372,2'-Azobis(2,4-dimethylvaleronitrile)HCID 712089357-fluoro-1-(2-fluoro-phenyl)-3-methyl-1H-quinolin-4-one

Product 1

HCID 712090683-azidomethyl-7-fluoro-1-(2-fluoro-phenyl)-1H-quinolin-4-oneYield 53.6%

Reagents, catalysts & solvents 1

HCID 5943Carbon TetrachlorideSolvent

Procedure

In a 50 mL round bottom flask, 7-fluoro-1-(2-fluoro-phenyl)-3-methyl-1H-quinolin-4-one (1.20 g, 4.42 mmol), N-bromosuccinimide (0.787 g, 4.42 mmol) and V65 [2,2′-azobis(2,4-dimethylvaleronitrile)](0.33 g, 1.33 mmol) were combined with carbon tetrachloride (35.0 mL). The reaction mixture was heated to reflux for 5 hr. The reaction was concentrated to dryness and the crude (containing 3-bromomethyl-7-fluoro-1-(2-fluoro-phenyl)-1H-quinolin-4-one) was redissolved in DMF (10.0 mL). To this reaction mixture was added sodium azide (1.44 g, 22.1 mmol) and the reaction was stirred at room temperature overnight. The reaction was partitioned between ethyl acetate and water and the organic layer was washed with saturated aqueous sodium bicarbonate solution. The organic layer was evaporated to dryness and purified by flash chromatography using 40% ethyl acetate-hexanes to afford 3-azidomethyl-7-fluoro-1-(2-fluoro-phenyl)-1H-quinolin-4-one (740 mg, 53.6%).

Workup

  1. temperatureThe reaction mixture was heated
  2. temperatureto reflux for 5 hr
  3. concentrationThe reaction was concentrated to dryness
  4. additionthe crude (containing 3-bromomethyl-7-fluoro-1-(2-fluoro-phenyl)-1H-quinolin-4-one)
  5. dissolutionwas redissolved in DMF (10.0 mL)
  6. customThe reaction was partitioned between ethyl acetate and water
  7. washthe organic layer was washed with saturated aqueous sodium bicarbonate solution
  8. customThe organic layer was evaporated to dryness
  9. custompurified by flash chromatography

Sources & evidence

ORD record
ord-c4229f9e53f0439f9ad7542f2fb8c7cf
Source dataset
uspto-grants-2013_08
Patent number
US08501732B2

Reaction notes

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