Triethylamine → 2-Chloro-5-(1-methanesulfonyl-piperidin-4-yloxy)-pyridine

HRID 1049041Notes

Reaction equation

HRID 1049041 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([O:8][CH:9]2[CH2:14][CH2:13][NH:12][CH2:11][CH2:10]2)=[CH:4][N:3]=1.CCN(CC)CC.[CH3:22][S:23](Cl)(=[O:25])=[O:24]>C(Cl)Cl>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([O:8][CH:9]2[CH2:14][CH2:13][N:12]([S:23]([CH3:22])(=[O:25])=[O:24])[CH2:11][CH2:10]2)=[CH:4][N:3]=1

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 31297Methanesulfonyl chlorideHCID 598623862-Chloro-5-(piperidin-4-yloxy)pyridine

Product 1

HCID 867218872-Chloro-5-(1-methanesulfonyl-piperidin-4-yloxy)-pyridineYield 51.3%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

A solution of 2-chloro-5-(piperidin-4-yloxy)-pyridine (4.55 g, 21.39 mmol) and Et3N (5.92 mL, 42.8 mmol) in DCM (50 mL) was treated with methanesulfonyl chloride (2.48 mL, 32.09 mmol) and stirred at room temperature for 2 hours. The mixture was diluted with DCM, washed with 1 N aqueous HCl, saturated aqueous NaHCO3, water and brine, dried over Na2SO4 and concentrated under vacuum. Purification by silica gel column chromatography (0-70% EtOAc in cyclohexane) gave 2-chloro-5-(1-methanesulfonyl-piperidin-4-yloxy)-pyridine (3.19 g, 51%). 1H NMR (300 MHz, CDCl3) δ 8.07 (d, J=2.9 Hz, 1H), 7.28-7.16 (m, 2H), 4.58-4.49 (m, 1H), 3.44-3.28 (m, 4H), 2.83 (s, 3H), 2.13-1.92 (m, 4H). LCMS (m/z, Method A) ES+ 290.9 [M+1]+.

Workup

  1. washwashed with 1 N aqueous HCl, saturated aqueous NaHCO3, water and brine
  2. dry with materialdried over Na2SO4
  3. concentrationconcentrated under vacuum
  4. customPurification by silica gel column chromatography (0-70% EtOAc in cyclohexane)

Sources & evidence

ORD record
ord-6656beabdfb743aaa04097d5d1b35282
Source dataset
uspto-grants-2016_07
Patent number
US09382222B2

Reaction notes

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