Dimethyl Sulfoxide → 1-Methyl-4-[(4-nitrophenoxy)methyl]piperidine

Temperature

70 °C

A mixture of 1-chloro-4-nitrobenzene (23) (2.37 g, 15.0 mmol), alcohol 22 (1.94 g, 15.0 mmol), and DMSO (25 mL) was treated portionwise with NaH (60% in mineral oil, 660 mg, 16.5 mmol) at 40° C. The mixture was stirred at 70° C. for 3 h, poured into water (150 mL), and extracted with Et2O (5×100 mL). The combined organic fractions were washed with water (250 mL) and brine (250 mL), dried (MgSO4), and the solvent was removed in vacuo. The resulting solid was recrystallized from Et2O to give 24 (3.12 g, 83%) as yellow needles. 1H NMR (300 MHz, CDCl3): δ=1.36-1.56 (m, 2 H, 3-Hax, 5-Hax), 1.75-1.91 (m, 3 H, 3-Heq, 4-H, 5-Heq), 1.98 (dt, J=11.9, 1.9 Hz, 2 H, 2-Hax, 6-Hax), 2.30 (s, 3 H, NMe), 2.85-2.98 (m, 2 H, 2-Heq, 6-Heq), 3.90 (d, J=5.8 Hz, 2 H, OCH2), 6.94 (mc, 2 H, 2′-H, 6′-H), 8.19 (mc, 2 H, 3′-H, 5′-H) ppm. —13C NMR (50.3 MHz, CDCl3): δ=28.9 (C-3, C-5), 35.1 (C-4), 46.4 (NMe), 55.3 (C-2, C-6), 73.3 (OCH2), 114.3 (C-2′, C-6′), 125.8 (C-3′, C-5′), 141.3 (C-4′), 164.1 (C-1′) ppm. −MS (70 eV, EI): m/z (%)=250 (79) [M]+, 249 (100) [M−H]+. —C13H18N2O3 (250.29): calcd. C, 62.38; H, 7.25; found C, 62.25; H, 7.40.

1. extractionextracted with Et2O (5×100 mL)
2. washThe combined organic fractions were washed with water (250 mL) and brine (250 mL)
3. dry with materialdried (MgSO4)
4. customthe solvent was removed in vacuo
5. customThe resulting solid was recrystallized from Et2O

ORD record

ord-ed5a5528274c4ac58b00c486421fb296

Source dataset

uspto-grants-2015_01

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08940784B2