Hydrochloric Acid → N-[2,4-difluoro-5-(4-piperidinyl)phenyl]-2-methylpropanamide

HRID 1269177Notes

Reaction equation

HRID 1269177 reaction equation
[F:1][C:2]1[CH:7]=[C:6]([F:8])[C:5]([NH:9][C:10](=[O:14])[CH:11]([CH3:13])[CH3:12])=[CH:4][C:3]=1[CH:15]1[CH2:20][CH2:19][N:18](C(OC(C)(C)C)=O)[CH2:17][CH2:16]1.Cl>O1CCOCC1>[F:8][C:6]1[CH:7]=[C:2]([F:1])[C:3]([CH:15]2[CH2:16][CH2:17][NH:18][CH2:19][CH2:20]2)=[CH:4][C:5]=1[NH:9][C:10](=[O:14])[CH:11]([CH3:12])[CH3:13]

Participants

4

Reactant 2

HCID 313Hydrochloric AcidHCID 16757165Tert-butyl 4-[2,4-difluoro-5-(isobutyrylamino)phenyl]-1-piperidinecarboxylate

Product 1

HCID 16757253N-[2,4-difluoro-5-(4-piperidinyl)phenyl]-2-methylpropanamideYield 98%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent2×

Procedure

Into a solution of tert-butyl 4-[2,4-difluoro-5-(isobutyrylamino)phenyl]-1-piperidinecarboxylate (6.54 g, 17.1 mmol) in 1,4-dioxane (40.0 mL) was added 4M HCl in 1,4-dioxane (160 mL) at room temperature. The reaction mixture was stirred for 1 h and concentrated in vacuo. The residue was dissolved in 100 mL of H2O and was basified with 10% KOH solution (50 mL). The aqueous layer was extracted with CHCl3/i-PrOH (3:1, 3×150 mL). The combined organic extracts were washed with brine, dried over MgSO4, filtered and concentrated in vacuo to give 4.72 g (16.7 mmol, 98%) of N-[2,4-difluoro-5-(4-piperidinyl)phenyl]-2-methylpropanamide: ESMS m/e: 283.3 (M+H)+.

Workup

  1. concentrationconcentrated in vacuo
  2. dissolutionThe residue was dissolved in 100 mL of H2O
  3. extractionThe aqueous layer was extracted with CHCl3/i-PrOH (3:1, 3×150 mL)
  4. washThe combined organic extracts were washed with brine
  5. dry with materialdried over MgSO4
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-f5f55f8ccd6640428929132d350fa9fc
Source dataset
uspto-grants-2007_04
Patent number
US07199135B2

Reaction notes

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