Potassium bis(trimethylsilyl)amide → 3-(9-chloro-3-methyl-4-oxo-5H-isoxazolo[4,3-c]quinolin-5-yl)-piperidine-1-carboxylic acid methyl ester

HRID 2212191

Reaction equation

HRID 2212191 reaction equation
C[Si]([N-][Si](C)(C)C)(C)C.[K+].[CH3:11][O:12][C:13]([N:15]1[CH2:20][CH2:19][CH2:18][CH:17]([NH:21][C:22]([C:24]2[C:25]([C:30]3[C:35](F)=[CH:34][CH:33]=[CH:32][C:31]=3[Cl:37])=[N:26][O:27][C:28]=2[CH3:29])=[O:23])[CH2:16]1)=[O:14]>CN(C)C=O>[CH3:11][O:12][C:13]([N:15]1[CH2:20][CH2:19][CH2:18][CH:17]([N:21]2[C:35]3[CH:34]=[CH:33][CH:32]=[C:31]([Cl:37])[C:30]=3[C:25]3=[N:26][O:27][C:28]([CH3:29])=[C:24]3[C:22]2=[O:23])[CH2:16]1)=[O:14]

Participants

4

Reactant 2

HCID 3251421Potassium bis(trimethylsilyl)amideHCID 69652389HCID 69652389, compound

Product 1

HCID 99515613-(9-chloro-3-methyl-4-oxo-5H-isoxazolo[4,3-c]quinolin-5-yl)-piperidine-1-carboxylic acid methyl esterYield 92.4%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

Add potassium bis(trimethylsilyl)-amide (5.5 mL, 2.73 mmol, 0.5 M in toluene) to a solution of 3-{[3-(2-chloro-6-fluoro-phenyl)-5-methyl-isoxazole-4-carbonyl]-amino}-piperidine-1-carboxylic acid methyl ester (0.72 g, 1.82 mmol) in dimethylformamide (56 mL). After 5 minutes, quench the reaction with 1N HCl and concentrate. Partition the resulting material between 20% isopropanol/chloroform and 1N HCl. Wash the organic layer with saturated aqueous sodium bicarbonate solution and brine, dry over magnesium sulfate, and concentrate. Purify by flash chromatography on silica gel (eluting with 0–0.5% methanol/chloroform) to give 632 mg of the title compound as a white solid, 92% yield. 1H NMR: consistent with structure. MS (ion spray) 376 (M+).

Workup

  1. customquench
  2. customthe reaction with 1N HCl
  3. concentrationconcentrate
  4. customPartition the resulting material between 20% isopropanol/chloroform and 1N HCl
  5. washWash the organic layer with saturated aqueous sodium bicarbonate solution and brine
  6. dry with materialdry over magnesium sulfate
  7. concentrationconcentrate
  8. customPurify by flash chromatography on silica gel (eluting with 0–0.5% methanol/chloroform)

Sources & evidence

ORD record
ord-98d59a58ccf449549ce5dfcde00cd7cb
Source dataset
uspto-grants-2006_09
Patent number
US07101891B2

Linked notes

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