Acetic Acid → 4-(4-Iodo-phenyl)-1-methyl-piperidine-4-carbonitrile

To a solution of the crude 4-(4-iodo-phenyl)-piperidine-4-carbonitrile (˜4.7 mmol) in ClCH2CH2Cl (100 mL) was added formaldehyde (1.92 mL of a 37% solution in H2O, 23.65 mmol, 5 eq.) and HOAc (1 mL, 1% v/v). The mixture was stirred for 0.5 h at room temperature and then NaBH(OAc)3 (1.48 g, 7 mmol, 1.5 eq.) was added. The reaction mixture was stirred for 16 h and then quenched by the addition of saturated aqueous NaHCO3 solution (50 mL). The resulting mixture was extracted with EtOAc (200 mL) and the organic layer was washed with saturated aqueous NaHCO3 solution (50 mL) and saturated brine (100 mL). The organic layer was dried over anhydrous Na2SO4, filtered and concentrated by rotary evaporation to give the crude 4-(4-iodo-phenyl)-1-methyl-piperidine-4-carbonitrile (1.5 g, 97%) as a brown oil. 1H NMR (300 MHz, CDCl3): δ 7.84 (dd, 2H), 7.36 (dd, 2H), 3.08 (dt, 2H), 2.60 (m, 2H), 2.50 (s, 3H), 2.20 (m, 4H).

1. stirringThe reaction mixture was stirred for 16 h
2. customquenched by the addition of saturated aqueous NaHCO3 solution (50 mL)
3. extractionThe resulting mixture was extracted with EtOAc (200 mL)
4. washthe organic layer was washed with saturated aqueous NaHCO3 solution (50 mL) and saturated brine (100 mL)
5. dry with materialThe organic layer was dried over anhydrous Na2SO4
6. filtrationfiltered
7. concentrationconcentrated by rotary evaporation

ORD record

ord-82b9363a8da14a85bf9a68abafa853de

Source dataset

uspto-grants-2005_05

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06887889B2