Ammonia → 1,1-Dimethylethyl 4-[4-(aminocarbonyl)phenyl]-1-piperidinecarboxylate

HRID 1756998Notes

Reaction equation

HRID 1756998 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([C:14]2[CH:19]=[CH:18][C:17]([C:20]([OH:22])=O)=[CH:16][CH:15]=2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].O[N:24]1C2C=CC=CC=2N=N1.C1(N=C=NC2CCCCC2)CCCCC1.N>CN(C)C=O>[NH2:24][C:20]([C:17]1[CH:18]=[CH:19][C:14]([CH:11]2[CH2:12][CH2:13][N:8]([C:6]([O:5][C:1]([CH3:4])([CH3:3])[CH3:2])=[O:7])[CH2:9][CH2:10]2)=[CH:15][CH:16]=1)=[O:22]

Participants

6

Reactant 4

HCID 222AmmoniaHCID 10868DicyclohexylcarbodiimideHCID 757711-HydroxybenzotriazoleHCID 224928594-(4-Carboxy-phenyl)-piperidine-1-carboxylic acid tert-butyl ester

Product 1

HCID 224929041,1-Dimethylethyl 4-[4-(aminocarbonyl)phenyl]-1-piperidinecarboxylate

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
-10 °C

Procedure

To a solution of 21.4 g of 1-tert.butyloxycarbonyl-4-(4-carboxyphenyl)-piperidine in 250 ml of anhydrous dimethylformamide are added, at -10° C., 9.5 g of 1-hydroxy-(1H)-benzotriazole and 17.3 g of N,N'-dicyclohexylcarbodiimide. The mixture is stirred for 15 minutes at -10° C. and the temperature is allowed to come up to ambient temperature within 1 hour. Then at -10° C. 20 ml of conc. ammonia are added dropwise with vigorous stirring. The mixture is stirred for 1 hour at -10° C. and for a further 2 hours at ambient temperature. The solvent is removed under reduced pressure. The residue remaining is suspended in water and the aqueous phase is extracted four times with ethyl acetate. The combined ethyl acetate phases are filtered, the filtrate is dried over sodium sulphate and the solvent is removed under reduced pressure. The residue remaining is chromatographed over silica gel. Yield: 17.5 g (82% of theory), Melting point: 188°-191° C. Rf value: 0.36 (silica gel; ethyl acetate/cyclohexane=4:1)

Workup

  1. waitto come up to ambient temperature within 1 hour
  2. customat -10° C
  3. stirringThe mixture is stirred for 1 hour at -10° C. and for a further 2 hours at ambient temperature
  4. customThe solvent is removed under reduced pressure
  5. extractionthe aqueous phase is extracted four times with ethyl acetate
  6. filtrationThe combined ethyl acetate phases are filtered
  7. dry with materialthe filtrate is dried over sodium sulphate
  8. customthe solvent is removed under reduced pressure
  9. customThe residue remaining is chromatographed over silica gel

Sources & evidence

ORD record
ord-c64ceee979524d0aa66dc4b5f81c93f4
Source dataset
uspto-grants-1995_08
Patent number
US05442064

Reaction notes

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