Sodium hydride → 5-Chloro-2-(piperidin-4-yloxy)pyridine

HRID 1244442Notes

Reaction equation

HRID 1244442 reaction equation
[H-].[Na+].Cl[C:4]1[CH:9]=[CH:8][C:7]([Cl:10])=[CH:6][N:5]=1.[OH:11][CH:12]1[CH2:17][CH2:16][NH:15][CH2:14][CH2:13]1>COCCOC>[NH:15]1[CH2:16][CH2:17][CH:12]([O:11][C:4]2[CH:9]=[CH:8][C:7]([Cl:10])=[CH:6][N:5]=2)[CH2:13][CH2:14]1

Participants

5

Reactant 3

HCID 24758Sodium hydride2×HCID 276852,5-DichloropyridineHCID 79341Piperidin-4-ol

Product 1

HCID 112643295-Chloro-2-(piperidin-4-yloxy)pyridine

Reagents, catalysts & solvents 1

HCID 80711,2-DimethoxyethaneSolvent2×

Conditions

Temperature
82 °C

Procedure

NaH (2.88 g, 66 mmol, 55% dispersion in mineral oil) was stirred in dry DME (200 ml), under Argon. A mixture of 2,5-dichloropyridine (8.87 g, 60 mmol) and 4-hydroxypiperidine (6.67 g, 66 mmol) dissolved in dry DME (200 ml) was added to the NaH suspension dropwise, over a period of 30 minutes. After complete addition the reaction is heated to 82° C. for 48 hrs, maintaining the Argon blanket. The reaction was slowly quenched with water before removing most of the THF. Extracted the aqueous with DCM (×3). The organic layers were dried with Na2SO4 and evaporated in vacuo to afford 2-(4-piperidinyloxy)-5-chloropyridine as a yellow oil (12.7 g, quantitative).

Workup

  1. additionAfter complete addition the reaction
  2. temperaturemaintaining the Argon blanket
  3. customThe reaction was slowly quenched with water
  4. custombefore removing most of the THF
  5. extractionExtracted the aqueous with DCM (×3)
  6. dry with materialThe organic layers were dried with Na2SO4
  7. customevaporated in vacuo

Sources & evidence

ORD record
ord-e6e201fbab1a4da5bd56586f149849e3
Source dataset
uspto-grants-2006_10
Patent number
US07122551B2

Reaction notes

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