Acetic Anhydride → 1-(2-(5-Amino-2-(4-fluoro-phenoxy)-phenyl)-piperidin-1-yl)-ethanone

HRID 13287Notes

Reaction equation

HRID 13287 reaction equation
[C:1](OC(=O)C)(=[O:3])[CH3:2].[F:8][C:9]1[CH:35]=[CH:34][C:12]([O:13][C:14]2[CH:19]=[CH:18][C:17]([NH:20]C(=O)OC(C)(C)C)=[CH:16][C:15]=2[C:28]2[CH:33]=[CH:32][CH:31]=[CH:30][N:29]=2)=[CH:11][CH:10]=1.[H][H].C(=O)(O)[O-].[Na+]>[C].[Pd].Cl.O1CCOCC1.C(O)C>[NH2:20][C:17]1[CH:18]=[CH:19][C:14]([O:13][C:12]2[CH:34]=[CH:35][C:9]([F:8])=[CH:10][CH:11]=2)=[C:15]([CH:28]2[CH2:33][CH2:32][CH2:31][CH2:30][N:29]2[C:1](=[O:3])[CH3:2])[CH:16]=1

Participants

8

Reactant 4

HCID 7918Acetic AnhydrideHCID 516892Sodium BicarbonateHCID 86619204t-Butyl (4-(4-fluoro-phenoxy)-3-pyridin-2-yl-phenyl)-carbamateHCID 178418361HCID 178418361, compound

Product 1

HCID 231451501-(2-(5-Amino-2-(4-fluoro-phenoxy)-phenyl)-piperidin-1-yl)-ethanone

Reagents, catalysts & solvents 3

HCID 178418390HCID 178418390, compoundCatalystHCID 702EthanolSolventHCID 204431481,4-Dioxane hydrochlorideSolvent

Procedure

0.3 ml of acetic anhydride and 100 mg of 10% palladium-carbon catalyst were added to an ethanol (20 ml) solution of 300 mg of t-butyl (4-(4-fluoro-phenoxy)-3-pyridin-2-yl-phenyl)-carbamate, and the reaction liquid was stirred overnight in a hydrogen atmosphere. The catalyst was removed through filtration through Celite, and the filtrate was distilled under reduced pressure to obtain a crude product. The resulting crude product was dissolved in 5 ml of 4 N hydrochloric acid/1,4-dioxane solution, and the reaction liquid was stirred at room temperature for 1 hour. Aqueous saturated sodium bicarbonate was added to the reaction liquid, and extracted with ethyl acetate. The organic layer was washed with saturated saline, and dried with anhydrous sodium sulfate. The solvent was evaporated away under reduced pressure, and the resulting residue was purified through silica gel column chromatography (developing solvent: hexane/ethyl acetate=1/1 to ethyl acetate) to obtain the entitled compound as a pale yellow solid.

Workup

  1. customthe reaction liquid
  2. customThe catalyst was removed through filtration through Celite
  3. distillationthe filtrate was distilled under reduced pressure
  4. customto obtain a crude product
  5. customthe reaction liquid
  6. extractionextracted with ethyl acetate
  7. washThe organic layer was washed with saturated saline
  8. dry with materialdried with anhydrous sodium sulfate
  9. customThe solvent was evaporated away under reduced pressure
  10. customthe resulting residue was purified through silica gel column chromatography (developing solvent: hexane/ethyl acetate=1/1 to ethyl acetate)

Sources & evidence

ORD record
ord-c0c038193d2143a48f5777bc075f973e
Source dataset
uspto-grants-2010_06
Patent number
US07728025B2

Reaction notes

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