Trifluoroacetic acid → 2,4,6-Trifluoro-N-[6-(piperidin-4-yloxy)pyridin-2-yl]-benzamide

HRID 1822037Notes

Reaction equation

HRID 1822037 reaction equation
FC(F)(F)C(O)=O.C(OC([N:15]1[CH2:20][CH2:19][CH:18]([O:21][C:22]2[CH:27]=[CH:26][CH:25]=[C:24]([NH:28][C:29](=[O:39])[C:30]3[C:35]([F:36])=[CH:34][C:33]([F:37])=[CH:32][C:31]=3[F:38])[N:23]=2)[CH2:17][CH2:16]1)=O)(C)(C)C.[OH-].[Na+]>C(Cl)Cl>[F:36][C:35]1[CH:34]=[C:33]([F:37])[CH:32]=[C:31]([F:38])[C:30]=1[C:29]([NH:28][C:24]1[CH:25]=[CH:26][CH:27]=[C:22]([O:21][CH:18]2[CH2:17][CH2:16][NH:15][CH2:20][CH2:19]2)[N:23]=1)=[O:39]

Participants

5

Reactant 3

HCID 6422Trifluoroacetic acidHCID 14798Sodium HydroxideHCID 578937794-[6-(2,4,6-Trifluoro-benzoylamino)-pyridin-2-yloxy]-piperidine-1-carboxylic acid tert-butyl ester

Product 1

HCID 578937702,4,6-Trifluoro-N-[6-(piperidin-4-yloxy)pyridin-2-yl]-benzamideYield 94%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

Add trifluoroacetic acid (20 mL) to a solution of 4-[6-(2,4,6-trifluoro-benzoylamino)-pyridin-2-yloxy]-piperidine-1-carboxylic acid tert-butyl ester (preparation 92, 2.482 g, 5.5 mmol) in methylene dichloride (50 mL) and stir for 30 min. Remove volatiles, dissolve the residue in methylene dichloride, adjust pH>11 with 1N NaOH, extract with methylene dichloride three times. Combine the organic layers, dry over Na2SO4, filter and concentrate to give a residue. Recrystallization (ethanol-H2O) provides 1.625 g of the title compound as a white solid. Concentrate themother liquor and further purify by chromatography (silica gel, eluting with 5.5% 2M NH3-methanol in CH2Cl2) to provide another 200 mg (total yield 94%) of the title compound: mass spectrum (ion spray): m/z=352.0 (M+1); 1H NMR (CDCl3, ppm): 8.35 (br, 1H), 7.68 (d, br, 1H), 7.46 (t, 1H), 6.60 (m, 2H), 6.34 (d, 1H), 4.84 (m, 1H), 2.93 (m, 2H), 2.59 (m, 2H), 1.85 (m, 2H), 1.46 (m, 3H).

Workup

  1. extractionextract with methylene dichloride three times
  2. dry with materialCombine the organic layers, dry over Na2SO4
  3. filtrationfilter
  4. concentrationconcentrate
  5. customto give a residue
  6. customRecrystallization (ethanol-H2O)

Sources & evidence

ORD record
ord-d81c1c85c27549f7bcd88f2be4219cc6
Source dataset
uspto-grants-2009_10
Patent number
US07608629B2

Reaction notes

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