Sodium Cyanide → Ethyl 4-cyano-4-(4-fluoroanilino)piperidine-1-carboxylate

HRID 1065256Notes

Reaction equation

HRID 1065256 reaction equation
O=[C:2]1[CH2:7][CH2:6][N:5]([C:8]([O:10][CH2:11][CH3:12])=[O:9])[CH2:4][CH2:3]1.[F:13][C:14]1[CH:19]=[CH:18][C:17]([NH2:20])=[CH:16][CH:15]=1.[C-:21]#[N:22].[Na+].[OH-].[NH4+]>ClC(Cl)Cl.O.C(O)(=O)C>[C:21]([C:2]1([NH:20][C:17]2[CH:18]=[CH:19][C:14]([F:13])=[CH:15][CH:16]=2)[CH2:7][CH2:6][N:5]([C:8]([O:10][CH2:11][CH3:12])=[O:9])[CH2:4][CH2:3]1)#[N:22]

Participants

8

Reactant 4

HCID 8929Sodium Cyanide2×HCID 97314-FluoroanilineHCID 14923Ammonium HydroxideHCID 34767Ethyl 4-oxo-1-piperidinecarboxylate

Product 1

HCID 3018977Ethyl 4-cyano-4-(4-fluoroanilino)piperidine-1-carboxylate

Reagents, catalysts & solvents 3

HCID 176Acetic AcidSolventHCID 962WaterSolvent2×HCID 6212ChloroformSolvent

Procedure

75 Parts of ethyl 4-oxo-1-piperidinecarboxylate and 50 parts of 4-fluorobenzeneamine are added dropwise to 220 parts of acetic acid. The whole is stirred for 30 minutes. Then there is added dropwise a solution of 23 parts of sodium cyanide in 65 parts of water at room temperature (exothermic reaction). Upon completion, a second portion of 2 parts of sodium cyanide is added and the whole is stirred overnight. The reaction mixture is poured onto a mixture of 440 parts of water, 440 parts of ammonium hydroxide solution and 525 parts of trichloromethane. The trichloromethane-phase is separated and the aqueous layer is extracted with trichloromethane. The combined organic layers are washed with water, dried and evaporated, yielding 127.5 parts of ethyl 4-cyano-4-(4-fluorophenylamino)-1-piperidinecarboxylate as a residue.

Workup

  1. custom(exothermic reaction)
  2. stirringthe whole is stirred overnight
  3. customThe trichloromethane-phase is separated
  4. extractionthe aqueous layer is extracted with trichloromethane
  5. washThe combined organic layers are washed with water
  6. customdried
  7. customevaporated

Sources & evidence

ORD record
ord-8c2b127313064b3d8add855603979ccb
Source dataset
uspto-grants-1982_05
Patent number
US04329353

Reaction notes

Loading…