Potassium bis(trimethylsilyl)amide → HCID 20729710, compound

HRID 352243Notes

Reaction equation

HRID 352243 reaction equation
[C:1]1([NH:7][CH2:8][CH2:9][C@@H:10]2[CH2:15][CH2:14][CH2:13][C@H:12]([NH:16][C:17]([C:19]3[C:20]([C:25]4[C:30](F)=[CH:29][CH:28]=[CH:27][C:26]=4[Cl:32])=[N:21][O:22][C:23]=3[CH3:24])=[O:18])[CH2:11]2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.C[Si]([N-][Si](C)(C)C)(C)C.[K+]>CN(C=O)C>[C:1]1([NH:7][CH2:8][CH2:9][C@@H:10]2[CH2:15][CH2:14][CH2:13][C@H:12]([N:16]3[C:30]4[CH:29]=[CH:28][CH:27]=[C:26]([Cl:32])[C:25]=4[C:20]4=[N:21][O:22][C:23]([CH3:24])=[C:19]4[C:17]3=[O:18])[CH2:11]2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1

Participants

4

Reactant 2

HCID 3251421Potassium bis(trimethylsilyl)amideHCID 20729738HCID 20729738, compound

Product 1

HCID 20729710HCID 20729710, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

N-{(1S,3S)-3-[2-(phenylamino)ethyl]cyclohexyl }[3-(2-chloro-6-fluorophenyl)-5-methylisoxazol-4-yl]carboxamide (54 mg; 0.118 mmol) was dissolved in anhydrous DMF (2 mL) under a dry nitrogen atmosphere at room temperature. When potassium bis(trimethylsilyl)amide (0.5 M in toluene; 572 μL; 2.2 equiv) was added dropwise to this solution, a clear orange color formed. After 5 min, the reaction was chilled in an ice bath, quenched with 1N HCl(aq) (10 mL), and extracted with ethyl acetate (twice). The organic layer was washed with saturated NaCl(aq) (once), dried with Na2SO4(s), filtered, and concentrated to dryness by rotary evaporation. The product was purified by radial chromatography on a 2 mm thick silica gel rotor. A dichloromethane mobile phase was ineffective at purifying the product. Re-chromatography with a 100% hexanes mobile phase followed by a 20% ethyl acetate/hexanes (v/v) mobile phase separated product from impurities. After drying from diethyl ether, an off-white foam (43 mg; 84%) was obtained.

Workup

  1. customa clear orange color formed
  2. temperaturethe reaction was chilled in an ice bath
  3. customquenched with 1N HCl(aq) (10 mL)
  4. extractionextracted with ethyl acetate (twice)
  5. washThe organic layer was washed with saturated NaCl(aq) (once),
  6. dry with materialdried with Na2SO4(s)
  7. filtrationfiltered
  8. concentrationconcentrated to dryness by rotary evaporation
  9. customThe product was purified by radial chromatography on a 2 mm thick silica gel rotor
  10. customat purifying the product
  11. customseparated product from impurities
  12. dry with materialAfter drying from diethyl ether
  13. customan off-white foam (43 mg; 84%) was obtained

Sources & evidence

ORD record
ord-1303a1ba13794236b47f0cfb3b60861d
Source dataset
uspto-grants-2004_06
Patent number
US06743794B2

Reaction notes

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