1-Chloro-4-nitrobenzene → 1-Methyl-4-[(4-nitrophenoxy)methyl]piperidine

HRID 2060922Notes

Reaction equation

Cl[C:2]1[CH:7]=[CH:6][C:5]([N+:8]([O-:10])=[O:9])=[CH:4][CH:3]=1.[CH3:11][N:12]1[CH2:17][CH2:16][CH:15]([CH2:18][OH:19])[CH2:14][CH2:13]1.[H-].[Na+]>CS(C)=O>[CH3:11][N:12]1[CH2:17][CH2:16][CH:15]([CH2:18][O:19][C:2]2[CH:7]=[CH:6][C:5]([N+:8]([O-:10])=[O:9])=[CH:4][CH:3]=2)[CH2:14][CH2:13]1

Participants

Conditions

Temperature: 40 °C

Procedure

To a mixture of p-chloro nitrobenzene (6.0 g, 38 mmol) and 1-methyl-4-piperidinemethanol (4.91 g, 38 mmol) in anhydrous DMSO (60 mL) was added NaH (1.82 g, 45.6 mmol) in small portions at room temperature under N2-atmosphere. After the addition was complete the reaction mixture was warmed at 40° C. and stirred for another 2 h. The reaction was quenched with water, and the product was extracted with EtOAc. The organic layer was washed with brine and dried over Na2SO4. The crude product was recrystallized from ether to yield 6.6 g (69%) of the title compound as an orange solid. 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 1.59-1.72 (m, 2H) 1.92 (d, J=11.37 Hz, 3 H) 2.19 (t, J=11.49 Hz, 2H) 2.44 (s, 3H) 3.09 (d, J=11.12 Hz, 2H) 3.93 (d, J=5.31 Hz, 2 H) 6.93 (d, J=9.2 Hz, 2H) 8.20 (d, J=9.6 Hz, 2H); [M+H] calc'd for C13H19N2O3, 251.2; found, 251.4.

Workup

additionAfter the addition
customThe reaction was quenched with water
extractionthe product was extracted with EtOAc
washThe organic layer was washed with brine
dry with materialdried over Na2SO4
customThe crude product was recrystallized from ether

Sources & evidence

ORD record: ord-b3f002c26efb4d63b9b2b07ae1a011f4
Source dataset: uspto-grants-2012_10
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08278450B2

Reaction notes

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