Potassium bis(trimethylsilyl)amide → 4-((6-Bromo-4-hydroxy-2-oxo-1,2-dihydroquinolin-3-yl)oxy)benzonitrile

HRID 520835Notes

Reaction equation

HRID 520835 reaction equation
[Br:1][C:2]1[CH:3]=[CH:4][C:5]([NH:12][C:13](=[O:24])[CH2:14][O:15][C:16]2[CH:21]=[CH:20][C:19]([C:22]#[N:23])=[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:24])[C:14]([O:15][C:16]1[CH:21]=[CH:20][C:19]([C:22]#[N:23])=[CH:18][CH:17]=1)=[C:7]2[OH:8]

Participants

5

Reactant 3

HCID 3251421Potassium bis(trimethylsilyl)amideHCID 8112554Methyl 5-bromo-2-(2-(4-cyanophenoxy)acetamido)benzoate2×HCID 18522661Acetone cardice

Product 1

HCID 867154554-((6-Bromo-4-hydroxy-2-oxo-1,2-dihydroquinolin-3-yl)oxy)benzonitrile

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a suspension of methyl 5-bromo-2-(2-(4-cyanophenoxy)acetamido)benzoate (0.240 g, 0.617 mmol, Intermediate 2: step b) in THF (6.65 mL) at −78° C. was added potassium bis(trimethylsilyl)amide (0.5 M in toluene, 3.66 mL, 1.83 mmol) over 1.5 minutes, and the mixture was stirred for 5 minutes. The dry-ice/acetone bath was replaced with wet-ice 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 was formed which was filtered and the solid was dried overnight in the air and 1 hour in an oven at 40° C. to give 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 was formed which
  6. filtrationwas filtered
  7. customthe solid was dried overnight in the air and 1 hour in an oven at 40° C.

Sources & evidence

ORD record
ord-958ee5eeb18142cb8afc3859721c2774
Source dataset
uspto-grants-2016_05
Patent number
US09328095B2

Reaction notes

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