Triethylamine → 4-[6-(2,4,6-Trifluoro-benzoylamino)-pyridin-2-yloxy]-piperidine-1-carboxylic acid tert-butyl ester

HRID 1822036Notes

Reaction equation

HRID 1822036 reaction equation
[F:1][C:2]1[CH:10]=[C:9]([F:11])[CH:8]=[C:7]([F:12])[C:3]=1[C:4](Cl)=[O:5].[C:13]([O:17][C:18]([N:20]1[CH2:25][CH2:24][CH:23]([O:26][C:27]2[CH:32]=[CH:31][CH:30]=[C:29]([NH2:33])[N:28]=2)[CH2:22][CH2:21]1)=[O:19])([CH3:16])([CH3:15])[CH3:14].C(N(CC)CC)C>C1COCC1.C(OCC)(=O)C>[C:13]([O:17][C:18]([N:20]1[CH2:25][CH2:24][CH:23]([O:26][C:27]2[CH:32]=[CH:31][CH:30]=[C:29]([NH:33][C:4](=[O:5])[C:3]3[C:2]([F:1])=[CH:10][C:9]([F:11])=[CH:8][C:7]=3[F:12])[N:28]=2)[CH2:22][CH2:21]1)=[O:19])([CH3:16])([CH3:14])[CH3:15]

Participants

6

Reactant 3

HCID 8471TriethylamineHCID 1448952,4,6-Trifluorobenzoyl chlorideHCID 578937944-(6-Amino-pyridin-2-yloxy)-piperidine-1-carboxylic acid tert-butyl ester

Product 1

HCID 578937794-[6-(2,4,6-Trifluoro-benzoylamino)-pyridin-2-yloxy]-piperidine-1-carboxylic acid tert-butyl esterYield 78.3%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
40 °C

Procedure

Add 2,4,6-trifluorobenzoyl chloride (1.64 g, 8.42 mmol) to a solution of 4-(6-amino-pyridin-2-yloxy)-piperidine-1-carboxylic acid tert-butyl ester (preparation 71, 2.06 g, 7.02 mmol) in triethylamine (1.066 g, 1.5 mL, 10.53 mmol) and THF (70 mL). Heat at 40° C. overnight. Dilute the mixture with ethyl acetate, wash with 0.1 N HCl, saturated NaHCO3 solution and saturated NaCl solution sequentially. Dry over Na2SO4, filter and concentrate to give a residue. Chromatography (silica gel) eluting with 14% ethyl acetate in hexanes provides 2.482 g (78%) of the title compound: mass spectrum (ion spray): m/z=452.1 (M+1); 1H NMR (CDCl3, ppm): 8.01 (s, br, 1H), 7.87 (d, br, 1H), 7.67 (t, 1H), 6.81 (m, 2H), 6.55 (d, 1H), 5.11 (m, 1H), 3.73 (m, 2H), 3.33 (m, 2H), 1.93 (m, 2H), 1.74 (m 2H), 1.49 (s, 9H).

Workup

  1. washwash with 0.1 N HCl, saturated NaHCO3 solution and saturated NaCl solution sequentially
  2. dry with materialDry over Na2SO4
  3. filtrationfilter
  4. concentrationconcentrate
  5. customto give a residue
  6. washChromatography (silica gel) eluting with 14% ethyl acetate in hexanes

Sources & evidence

ORD record
ord-63fe836a1dde4b9aa12547421e922fcf
Source dataset
uspto-grants-2009_10
Patent number
US07608629B2

Reaction notes

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