Trifluoroacetic acid → 2-Chloro-5-(piperidin-4-yloxy)pyridine

HRID 1049040Notes

Reaction equation

HRID 1049040 reaction equation
C(OC([N:8]1[CH2:13][CH2:12][CH:11]([O:14][C:15]2[CH:16]=[N:17][C:18]([Cl:21])=[CH:19][CH:20]=2)[CH2:10][CH2:9]1)=O)(C)(C)C.C(O)(C(F)(F)F)=O>C(Cl)Cl>[Cl:21][C:18]1[CH:19]=[CH:20][C:15]([O:14][CH:11]2[CH2:12][CH2:13][NH:8][CH2:9][CH2:10]2)=[CH:16][N:17]=1

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 86696180Tert-butyl 4-((6-chloropyridin-3-yl)oxy)piperidine-1-carboxylate

Product 1

HCID 598623862-Chloro-5-(piperidin-4-yloxy)pyridineYield 118.6%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A solution of 4-(6-chloro-pyridin-3-yloxy)-piperidine-1-carboxylic acid tert-butyl ester (5.68 g, 18.16 mmol) in DCM (2 mL) was treated with TFA (25 mL) and stirred at room temperature for 1 hour. The mixture was concentrated under vacuum, dissolved in 1 N aqueous HCl and washed with EtOAc. The aqueous a phase was basified with ammonium hydroxide and extracted into EtOAc. The combined extracts were dried over Na2SO4 and concentrated under vacuum to give 2-chloro-5-(piperidin-4-yloxy)-pyridine (4.58 g) as a yellow solid. 1H NMR (300 MHz, DMSO) δ 8.54 (br s, 1H), 8.18 (d, J=3.1 Hz, 1H), 7.60-7.53 (m, 1H), 7.45 (d, J=8.8 Hz, 1H), 4.76-4.65 (m, 1H), 3.30-3.19 (m, 2H), 3.11-3.00 (m, 2H), 2.15-2.03 (m, 2H), 1.89-1.74 (m, 2H). LCMS (m/z, Method A) ES+ 213.1 [M+1]+.

Workup

  1. concentrationThe mixture was concentrated under vacuum
  2. dissolutiondissolved in 1 N aqueous HCl
  3. washwashed with EtOAc
  4. extractionextracted into EtOAc
  5. dry with materialThe combined extracts were dried over Na2SO4
  6. concentrationconcentrated under vacuum

Sources & evidence

ORD record
ord-1c067101120941e59034038bac8b2fb7
Source dataset
uspto-grants-2016_07
Patent number
US09382222B2

Reaction notes

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