Ethanol → Tert-butyl 5-chlorospiro[indole-3,4'-piperidine]-1'-carboxylate

HRID 529050Notes

Reaction equation

HRID 529050 reaction equation
C(O)(C(F)(F)F)=O.[CH:8]([CH:10]1[CH2:15][CH2:14][N:13]([C:16]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17])[CH2:12][CH2:11]1)=O.Cl.[Cl:24][C:25]1[CH:30]=[CH:29][C:28]([NH:31]N)=[CH:27][CH:26]=1.C(O)C>C(Cl)(Cl)Cl>[Cl:24][C:25]1[CH:26]=[C:27]2[C:10]3([CH2:15][CH2:14][N:13]([C:16]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17])[CH2:12][CH2:11]3)[CH:8]=[N:31][C:28]2=[CH:29][CH:30]=1

Participants

6

Reactant 4

HCID 702EthanolHCID 6422Trifluoroacetic acidHCID 71600Hydrazine, (4-chlorophenyl)-, hydrochloride (1:1)HCID 1514430tert-Butyl 4-formylpiperidine-1-carboxylate

Product 1

HCID 67374111Tert-butyl 5-chlorospiro[indole-3,4'-piperidine]-1'-carboxylate

Reagents, catalysts & solvents 1

HCID 6212ChloroformSolvent

Conditions

Temperature
50 °C

Procedure

TFA (2.2 ml, 28 mmol) was added to a stirred solution of tert-butyl 4-formylpiperidine-1-carboxylate (2.00 g, 9.38 mmol), 1-(4-chlorophenyl)hydrazine hydrochloride (1.68 g, 9.38 mmol) and ethanol (0.2 mL) in CHCl3 (200 mL) at about 0° C. The reaction mixture was then stirred at about 50° C. overnight. After cooling, the reaction was quenched by the addition of 10% NH4OH (20 mL) and ice (60 mL). The organic layer was separated. The aqueous layer was extracted with DCM. The combined organic layers were washed with brine, dried over MgSO4, filtered and concentrated to yield tert-butyl 5-chlorospiro[indole-3,4′-piperidine]-1′-carboxylate which was used in the next step without further purification (2.57 g, 85%). LCMS (APCI+) m/z 221, 223 [M+H−Boc]+; Rt=3.67 min.

Workup

  1. temperatureAfter cooling
  2. customthe reaction was quenched by the addition of 10% NH4OH (20 mL) and ice (60 mL)
  3. customThe organic layer was separated
  4. extractionThe aqueous layer was extracted with DCM
  5. washThe combined organic layers were washed with brine
  6. dry with materialdried over MgSO4
  7. filtrationfiltered
  8. concentrationconcentrated

Sources & evidence

ORD record
ord-d55334eaedfa4b8fbf9baf7ea46f40c6
Source dataset
uspto-grants-2016_05
Patent number
US09346805B2

Reaction notes

Loading…