Acetyl chloride → N-[6-(1-Methyl-piperidin-4-yloxy)-pyridin-2-yl]-acetamide

HRID 1822013Notes

Reaction equation

[C:1](Cl)(=[O:3])[CH3:2].[CH3:5][N:6]1[CH2:11][CH2:10][CH:9]([O:12][C:13]2[N:18]=[C:17]([NH2:19])[CH:16]=[CH:15][CH:14]=2)[CH2:8][CH2:7]1.C(N(CC)CC)C>C1COCC1>[CH3:5][N:6]1[CH2:7][CH2:8][CH:9]([O:12][C:13]2[N:18]=[C:17]([NH:19][C:1](=[O:3])[CH3:2])[CH:16]=[CH:15][CH:14]=2)[CH2:10][CH2:11]1

Participants

Conditions

Temperature: 40 °C

Procedure

Add acetyl chloride (118 mg, 0.11 mL, 1.50 mmol) slowly to a solution of 6-(1-methyl-piperidin-4-yloxy)-pyridin-2-ylamine (preparation 72, 260 mg, 1.25 mmol) in triethylamine (190 mg, 0.26 mL, 1.88 mmol) and THF (10 mL), heat at 40° C. overnight. Quench the reaction with 0.1N NaOH, extract with methylene dichloride three times. Combine the organic layers, dry over Na2SO4, filter and concentrate to give a residue. Chromatography (silica gel) eluting with 4.5% 2M NH3-methanol in methylene dichloride provides 238 mg (76%) of the title compound as an oil: mass spectrum (ion spray): m/z=250.0 (M+1); 1H NMR (CDCl3, ppm): 7.70 (m, 2H), 7.56 (t, 1H), 6.44 (d, 1H), 4.91 (m, 1H), 2.68 (m, 2H), 2.34 (m, 5H), 2.20 (s, 3H), 2.00 (m, 2H), 1.81 (m, 2H).

Workup

customQuench
customthe reaction with 0.1N NaOH
extractionextract with methylene dichloride three times
dry with materialCombine the organic layers, dry over Na2SO4
filtrationfilter
concentrationconcentrate
customto give a residue
washChromatography (silica gel) eluting with 4.5% 2M NH3-methanol in methylene dichloride

Sources & evidence

ORD record: ord-12b803591a58435889dc875c76a163ce
Source dataset: uspto-grants-2009_10
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07608629B2

Reaction notes

Loading…