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

HRID 1392149Notes

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

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). 1H NMR (DMSO): 8.17 (d, 1H), 7.76 (dd, 1H), 6.81 (d, 1H), 4.96 (m, 1H), 2.93 (m, 2H), 2.53 (m, 2H), 1.91 (m, 2H), 1.46 (m, 2H); MS (ES+): 213.3 (MH+), 225.3 (MNa+)

Workup

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

Sources & evidence

ORD record: ord-298cd7b146ef48d8a27be31a4551c142
Source dataset: uspto-grants-2008_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07342020B2

Reaction notes

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