Potassium Hydroxide → 1-(4-Methoxy-benzyl)-3-propyl-piperidine

HRID 228494Notes

Reaction equation

[CH3:1][O:2][C:3]1[CH:19]=[CH:18][C:6]([CH2:7][N:8]2[CH2:13][CH2:12][CH2:11][CH:10]([C:14](=O)[CH2:15][CH3:16])[CH2:9]2)=[CH:5][CH:4]=1.[OH-].[K+].O.NN.[NH4+].[Cl-]>C(O)COCCO>[CH3:1][O:2][C:3]1[CH:4]=[CH:5][C:6]([CH2:7][N:8]2[CH2:13][CH2:12][CH2:11][CH:10]([CH2:14][CH2:15][CH3:16])[CH2:9]2)=[CH:18][CH:19]=1

Participants

Conditions

Temperature: 120 °C

Procedure

Combine 1-[1-(4-Methoxy-benzyl)-piperidin-3-yl]-propan-1-one (277.3 mg, 1.07 mmol), Diethylene glycol (10 mL), KOH (178.0 mg, 3.18 mmol), and Hydrazine-monohydrate (1.0 mL) at room temperature under a Nitrogen atmosphere. Heat the reaction mixture to 120° C. for 2 hours and then 220° C. for 4 hours. Cool reaction to room temperature and then pour the reaction mixture over sat NH4Cl (aq). Extract with Ethyl acetate, wash with brine, and dry over Na2SO4. Concentrate under reduced pressure and flash chromatograph using 3% 1N NH3 MeOH in CH2Cl2 to give 105.2 mg (40% yield) of the title compound: 1H NMR (500 MHz, CDCl3); 0.9 (3H, t), 1.1-1.4 (4H, m), 1.5-1.7 (3H, m), 1.7 (1H, d), 1.9 (1H, td), 2.7-2.9 (2H, m), 3.5 (2H, dd), 3.8 (3H, s), 6.8 (2H, d), 7.2 (2H, d); MS m/z 248 (M+1).

Workup

customat room temperature
temperatureCool
customreaction to room temperature
additionpour the reaction mixture
extractionExtract with Ethyl acetate
washwash with brine
dry with materialdry over Na2SO4
concentrationConcentrate under reduced pressure and flash chromatograph

Sources & evidence

ORD record: ord-e7a839a9a9434c49a918c0c32d82239f
Source dataset: uspto-grants-2009_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07560463B2

Reaction notes

Loading…