Sodium hydride → 2-[(1-Methyl-4-piperidinyl)oxy]-5-nitropyridine

HRID 2273081Notes

Reaction equation

[H-].[Na+].Cl[C:4]1[CH:9]=[CH:8][C:7]([N+:10]([O-:12])=[O:11])=[CH:6][N:5]=1.[OH:13][CH:14]1[CH2:19][CH2:18][N:17]([CH3:20])[CH2:16][CH2:15]1>C1COCC1>[CH3:20][N:17]1[CH2:18][CH2:19][CH:14]([O:13][C:4]2[CH:9]=[CH:8][C:7]([N+:10]([O-:12])=[O:11])=[CH:6][N:5]=2)[CH2:15][CH2:16]1

Participants

Conditions

Temperature: 0 °C

Procedure

557 mg of NaH (14 mmol) suspended in 10 ml of THF are placed under nitrogen. The mixture is cooled to 0° C. and a solution of 1.5 g (9.3 mmol) of 2-chloro-5-nitropyridine and 1.28 g (11.1 mmol) of 4-hydroxy-1-methylpiperidine in 15 ml of THF is added dropwise. The reaction mixture is refluxed for 4 hours. After hydrolysing the excess NaH, the solvent is evaporated off under reduced pressure. The residue is taken up in ethyl acetate and washed with water and then with saturated NaCl solution. It is then dried over Na2SO4 and filtered, and the filtrate is evaporated under reduced pressure. The residue is chromatographed on silica gel, eluting with a DCM/MeOH mixture from (100/0 v/v) up to 100/4 v/v) to give 1.1 g of 2-(1-methylpiperidin-4-yloxy)-5-nitropyridine.

Workup

temperatureThe reaction mixture is refluxed for 4 hours
customthe solvent is evaporated off under reduced pressure
washwashed with water
dry with materialIt is then dried over Na2SO4
filtrationfiltered
customthe filtrate is evaporated under reduced pressure
customThe residue is chromatographed on silica gel
washeluting with a DCM/MeOH mixture from (100/0 v/v) up to 100/4 v/v)

Sources & evidence

ORD record: ord-4d9e1ae15a884949b0e7493e37eef7ff
Source dataset: uspto-grants-2015_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09120812B2

Reaction notes

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