4-Iodophenylacetonitrile → 4-Cyano-4-(4-iodo-phenyl)-piperidine-1-carboxylic acid tert-butyl ester

HRID 2180159Notes

Reaction equation

HRID 2180159 reaction equation
[I:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][C:9]#[N:10])=[CH:4][CH:3]=1.[C:11]([O:15][C:16](=[O:24])[N:17]([CH2:21][CH2:22]Cl)[CH2:18][CH2:19]Cl)([CH3:14])([CH3:13])[CH3:12]>CS(C)=O.CCOC(C)=O>[C:11]([O:15][C:16]([N:17]1[CH2:21][CH2:22][C:8]([C:9]#[N:10])([C:5]2[CH:6]=[CH:7][C:2]([I:1])=[CH:3][CH:4]=2)[CH2:19][CH2:18]1)=[O:24])([CH3:14])([CH3:13])[CH3:12]

Participants

5

Reactant 2

HCID 1428664-IodophenylacetonitrileHCID 11230235N-BOC-N,N-Bis(2-chloroethyl)amine

Product 1

HCID 207794754-Cyano-4-(4-iodo-phenyl)-piperidine-1-carboxylic acid tert-butyl esterYield 67%

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of 4-iodophenylacetonitrile (6.88 g, 28.3 mmol, 1 eq.) and bis-(2-chloro-ethyl)-carbamic acid tert-butyl ester (7.2 g, 30 mmol, 1.05 eq.) in DMSO (100 mL) under argon (Ar) was added NaNH2 (2.46 g, 60 mmol, 2 eq.) in portions over 15 min. The reaction was stirred at room temperature for 0.5 h, then poured onto ice (200 g), diluted with EtOAc (250 mL) and stirred for 1 h. The organic layer was separated and the aqueous layer was washed repeatedly with EtOAc until colorless. The combined organic extracts were dried over anhydrous Na2SO4, filtered and concentrated by rotary evaporation to afford an orange oil which was purified by flash column chromatography by eluting with 7-12% EtOAc/hexanes to yield 4-cyano-4-(4-iodo-phenyl)-piperidine-1-carboxylic acid tert-butyl ester as a pale orange oil/solid (8.28 g, 18.96 mmol, 67%). 1H NMR (300 MHz, CDCl3): δ 7.82 (dd, 2H), 7.26 (dd, 2H), 4.38 (br. s, 2H), 4.28 (br. t, 2H), 2.15 (m, 2H), 2.0 (td, 2H), 1.59 (s, 9H). (Ref.: D. Gnecco et al, Org. Prep. Proceed. Int., (1996) 28 (4), 478-480.

Workup

  1. additionpoured onto ice (200 g)
  2. stirringstirred for 1 h
  3. customThe organic layer was separated
  4. washthe aqueous layer was washed repeatedly with EtOAc until colorless
  5. dry with materialThe combined organic extracts were dried over anhydrous Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated by rotary evaporation
  8. customto afford an orange oil which
  9. customwas purified by flash column chromatography
  10. washby eluting with 7-12% EtOAc/hexanes

Sources & evidence

ORD record
ord-7f62dd341d3b428faf2307d5e9b2dee8
Source dataset
uspto-grants-2005_05
Patent number
US06887889B2

Reaction notes

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