Hydrochloric Acid → 6-bromo-5-hydroxy-4-(trifluoromethyl)-1H-quinolin-2-one

HRID 1350134Notes

Reaction equation

HRID 1350134 reaction equation
[OH:1][C:2]1[CH:11]=[CH:10][CH:9]=[C:8]2[C:3]=1[C:4]([C:13]([F:16])([F:15])[F:14])=[CH:5][C:6](=[O:12])[NH:7]2.C(NC(C)C)(C)C.[Br:24]N1C(=O)CCC1=O.Cl>CCOC(C)=O>[Br:24][C:11]1[C:2]([OH:1])=[C:3]2[C:8](=[CH:9][CH:10]=1)[NH:7][C:6](=[O:12])[CH:5]=[C:4]2[C:13]([F:16])([F:14])[F:15]

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 7912DiisopropylamineHCID 67184N-bromobutanimideHCID 210943825-hydroxy-4-(trifluoromethyl)-1H-quinolin-2-one

Product 1

HCID 210943856-bromo-5-hydroxy-4-(trifluoromethyl)-1H-quinolin-2-oneYield 77%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent2×

Procedure

To a solution of 5-hydroxy-4-(trifluoromethyl)-1H-quinolin-2-one (4.38 g, 19.1 mmol) and diisopropylamine (14 mL, 100 mmol) in 100 mL EtOAc was added a solution of N-bromosuccinimide (3.74 g, 21.0 mmol) in 70 mL EtOAc at −10° C. over 30 min. The reaction mixture was stirred for 1 h, then acidified to pH 1 by the addition of 6M HCl. The mixture was extracted with EtOAc (3×150 mL) and the combined organic layers were washed with brine (200 mL), dried over MgSO4, filtered and concentrated under reduced pressure. Recrystallization from chloroform:hexanes afforded 4.5 g (77%) of 6-bromo-5-hydroxy-4-(trifluoromethyl)-1H-quinolin-2-one, an off-white solid. Rf0.4 (1:1 EtOAc:hexanes); 1H NMR (400 MHz, acetone-d6) δ 11.1 (broad s, 1H), 8.75 (broad s, 1H), 7.76 (d, 1H, J=8.8), 7.04 (d, 1H, J=8.8), 6.98 (s, 1H).

Workup

  1. extractionThe mixture was extracted with EtOAc (3×150 mL)
  2. washthe combined organic layers were washed with brine (200 mL)
  3. dry with materialdried over MgSO4
  4. filtrationfiltered
  5. concentrationconcentrated under reduced pressure
  6. customRecrystallization from chloroform

Sources & evidence

ORD record
ord-cc7dee57584c4864a91dd7e9601a2bb8
Source dataset
uspto-grants-2007_05
Patent number
US07214690B2

Reaction notes

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