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

HRID 2279561Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 2279561
[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]

Komponenten

8

Edukt 6

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

Produkt 1

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

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6228DimethylformamideLösungsmittel2×

Versuchsvorschrift

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.

Aufarbeitung

  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)

Quellen und Nachweise

ORD-Eintrag
ord-8874d655267d4af8b81e099e585c9895
Quelldatensatz
uspto-grants-2015_09
Patentnummer
US09133187B2

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