Sodium Iodide → tert-Butyl 4-cyano-4-(3,4-dichlorophenyl)piperidine-1-carboxylate

HRID 2279561Notes

Reaction equation

HRID 2279561 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([CH2:9][C:10]#[N:11])[CH:5]=[CH:6][C:7]=1[Cl:8].C1OCCOCCOCCOCCOC1.[H-].[Na+].[Na+].[I-].Cl[CH2:32][CH2:33][N:34]([CH2:42][CH2:43]Cl)[C:35](=[O:41])[O:36][C:37]([CH3:40])([CH3:39])[CH3:38].[NH4+].[Cl-]>CN(C=O)C>[C:10]([C:9]1([C:4]2[CH:5]=[CH:6][C:7]([Cl:8])=[C:2]([Cl:1])[CH:3]=2)[CH2:43][CH2:42][N:34]([C:35]([O:36][C:37]([CH3:39])([CH3:38])[CH3:40])=[O:41])[CH2:33][CH2:32]1)#[N:11]

Participants

8

Reactant 6

HCID 5238Sodium IodideHCID 24758Sodium hydrideHCID 25517Ammonium ChlorideHCID 3633615-Crown-5HCID 76690(3,4-Dichlorophenyl)acetonitrileHCID 11230235N-BOC-N,N-Bis(2-chloroethyl)amine

Product 1

HCID 49760263tert-Butyl 4-cyano-4-(3,4-dichlorophenyl)piperidine-1-carboxylateYield 68%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

To a stirred solution of 2-(3,4-dichlorophenyl)acetonitrile (3.50 g, 18.8 mmol, CASRN 3218-49-3) and 15-crown-5 (0.414 g, 1.88 mmol) in DMF (75 mL) at 0° C. under nitrogen was added NaH (1.88 g, 47.0 mmol, 60% mineral oil dispersion) in 2 portions. The reaction mixture was warmed to RT and stirred 35 min then re-cooled to 0° C. NaI (2.82 g, 18.8 mmol) was added followed by a solution of freshly prepared tert-butyl bis-(2-chloroethyl)carbamate (4.56 g, 18.8 mmol) in DMF (10 mL) via syringe. The reaction mixture was warmed to RT and stirred overnight. The reaction mixture was then poured into ice cold sat'd. NH4Cl solution (250 mL) with stirring and the mixture was extracted with EtOAc (2×250 mL). The combined extracts were dried (MgSO4), filtered and concentrated. The crude product was loaded onto a SiO2 column (Biotage 40L) and eluted with hexanes/EtOAc (6/1) to afford 4.54 g (68%) of tert-butyl 4-cyano-4-(3,4-dichlorophenyl)piperidine-1-carboxylate (356) as an off white solid.

Workup

  1. temperaturethen re-cooled to 0° C
  2. temperatureThe reaction mixture was warmed to RT
  3. stirringstirred overnight
  4. additionThe reaction mixture was then poured into ice cold sat'd
  5. extractionthe mixture was extracted with EtOAc (2×250 mL)
  6. dry with materialThe combined extracts were dried (MgSO4)
  7. filtrationfiltered
  8. concentrationconcentrated
  9. washeluted with hexanes/EtOAc (6/1)

Sources & evidence

ORD record
ord-8874d655267d4af8b81e099e585c9895
Source dataset
uspto-grants-2015_09
Patent number
US09133187B2

Reaction notes

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