Potassium bis(trimethylsilyl)amide → 6-Bromo-3-(4-chlorophenoxy)-4-hydroxyquinolin-2(1H)-one

HRID 520844Notes

Reaction equation

HRID 520844 reaction equation
[Br:1][C:2]1[CH:3]=[CH:4][C:5]([NH:12][C:13](=[O:23])[CH2:14][O:15][C:16]2[CH:21]=[CH:20][C:19]([Cl:22])=[CH:18][CH:17]=2)=[C:6]([CH:11]=1)[C:7](OC)=[O:8].C[Si]([N-][Si](C)(C)C)(C)C.[K+].C(=O)=O.CC(C)=O>C1COCC1>[Br:1][C:2]1[CH:11]=[C:6]2[C:5](=[CH:4][CH:3]=1)[NH:12][C:13](=[O:23])[C:14]([O:15][C:16]1[CH:21]=[CH:20][C:19]([Cl:22])=[CH:18][CH:17]=1)=[C:7]2[OH:8]

Participants

5

Reactant 3

HCID 3251421Potassium bis(trimethylsilyl)amideHCID 7765743Methyl 5-bromo-2-(2-(4-chlorophenoxy)acetamido)benzoateHCID 18522661Acetone cardice

Product 1

HCID 867154546-Bromo-3-(4-chlorophenoxy)-4-hydroxyquinolin-2(1H)-one

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a suspension of methyl 5-bromo-2-(2-(4-chlorophenoxy)acetamido)benzoate (5.15 g, 12.9 mmol, Intermediate 7: step a) in THF (140 mL) at −78° C. was added potassium bis(trimethylsilyl)amide (0.5 M in toluene, 76.7 mL, 38.4 mmol) over 4 minutes, and the mixture was stirred for 5 minutes. The dry-ice/acetone bath was replaced an with an ice-water bath and the reaction was stirred for 1.5 hours. The reaction was then quenched with water and ethyl acetate was added. The organic layer was removed and the aqueous layer was acidified with 2 N HCl (kept pH above 2). An off-white precipitate formed which was filtered and the solid was dried overnight in the air to yield the title compound.

Workup

  1. stirringthe reaction was stirred for 1.5 hours
  2. customThe reaction was then quenched with water and ethyl acetate
  3. additionwas added
  4. customThe organic layer was removed
  5. customAn off-white precipitate formed which
  6. filtrationwas filtered
  7. customthe solid was dried overnight in the air

Sources & evidence

ORD record
ord-5de976759283471abfa7338119820d63
Source dataset
uspto-grants-2016_05
Patent number
US09328095B2

Reaction notes

Loading…