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

Temperature

20 °C

To a solution of 4-iodophenylacetonitrile (10 g, 41.1 mmol) in anhydrous DMSO (20 mL) was added NaNH2 (4.8 g, 123.3 mmol, 3 eq.) in one portion. The temperature of the reaction was maintained at 20° C. using a water bath. The mixture was stirred at 20° C. for 20 min to give a deep red solution then a solution of bis-(2-chloro-ethyl)-methyl-amine.HCl salt (7.92 g, 41.1 mmol, 1 eq.) in anhydrous DMSO (20 mL) was added in a drop-wise fashion. The resulting mixture was stirred at room temperature for 16 h then partitioned between EtOAc (250 mL) and H2O (250 mL). The organic layer was separated and washed with H2O (3×100 mL) and saturated brine (100 mL) then dried over Na2SO4, filtered and concentrated by rotary evaporation. The crude product was purified by flash column chromatography by eluting with 10% MeOH/EtOAc to yield 4-(4-iodo-phenyl)-1-methyl-piperidine-4-carbonitrile as a brownish solid (7.6 g, 23.43 mmol, 57%). 1H NMR (300 MHz, CD3OD): δ 7.89 (d, 2H), 7.43 (d, 2H), 3.13 (d, 2H), 2.58 (td, 2H), 2.50 (s, 3H), 2.24 (m, 4H).

1. customto give a deep red solution
2. stirringThe resulting mixture was stirred at room temperature for 16 h
3. customthen partitioned between EtOAc (250 mL) and H2O (250 mL)
4. customThe organic layer was separated
5. washwashed with H2O (3×100 mL) and saturated brine (100 mL)
6. dry with materialthen dried over Na2SO4
7. filtrationfiltered
8. concentrationconcentrated by rotary evaporation
9. customThe crude product was purified by flash column chromatography
10. washby eluting with 10% MeOH/EtOAc

ORD record

ord-9000dbc2bb3e4431bec344935ea6db9d

Source dataset

uspto-grants-2005_05

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06887889B2