Phenylacetic Acid → tert-butyl (2S)-2-[(Z)-N'-(2-phenylacetyl)oxycarbamimidoyl]piperidine-1-carboxylate

HRID 397645Notes

Reaction equation

HRID 397645 reaction equation
O.ON1C2C=CC=CC=2N=N1.[C:12]1([CH2:18][C:19]([OH:21])=[O:20])[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1.CN1CCOCC1.Cl.CN(C)CCCN=C=NCC.[NH2:41]/[C:42](=[N:56]\O)/[C@@H:43]1[CH2:48][CH2:47][CH2:46][CH2:45][N:44]1[C:49]([O:51][C:52]([CH3:55])([CH3:54])[CH3:53])=[O:50]>CN(C)C1C=CN=CC=1.ClCCl.C(O)(=O)CC(CC(O)=O)(C(O)=O)O>[NH2:56]/[C:42](=[N:41]\[O:20][C:19](=[O:21])[CH2:18][C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1)/[C@@H:43]1[CH2:48][CH2:47][CH2:46][CH2:45][N:44]1[C:49]([O:51][C:52]([CH3:54])([CH3:53])[CH3:55])=[O:50]

Participants

9

Reactant 5

HCID 999Phenylacetic AcidHCID 79724-MethylmorpholineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 27960291-Hydroxybenzotriazole hydrateHCID 59085902tert-butyl (2S)-2-[(Z)-N'-hydroxycarbamimidoyl]piperidine-1-carboxylate

Product 1

HCID 59085894tert-butyl (2S)-2-[(Z)-N'-(2-phenylacetyl)oxycarbamimidoyl]piperidine-1-carboxylateYield 91.3%

Reagents, catalysts & solvents 3

HCID 142844-(Dimethylamino)pyridineCatalystHCID 311Citric AcidSolventHCID 6344DichloromethaneSolvent2×

Procedure

1-Hydroxybenzotriazole hydrate (8.67 g), phenylacetic acid (8.0 g), N-methylmorpholine (14.69 ml), 4-dimethylaminopyridine (3.3 g) and 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (12.29 g) were added to a solution of tert-butyl (Z)-(2S)-2-[amino(hydroxyimino)methyl]-1-piperidinecarboxylate (13.0 g) [see Preparation 4] in dichloromethane (180 ml). The reaction mixture was stirred for 2 hours under an atmosphere of nitrogen, after which time the mixture was diluted with dichloromethane and 1N aqueous citric acid solution. The organic layer was separated, washed with saturated aqueous sodium hydrogen carbonate solution, dried over magnesium sulphate and the solvent was removed under reduced pressure to afford tert-butyl (Z)-(2S)-2-(amino[(2-phenylacetyl)oxy]iminomethyl)-1-piperidinecarboxylate (17.63 g) as a white solid.

Workup

  1. customThe organic layer was separated
  2. washwashed with saturated aqueous sodium hydrogen carbonate solution
  3. dry with materialdried over magnesium sulphate
  4. customthe solvent was removed under reduced pressure

Sources & evidence

ORD record
ord-cec9c0ea11454573afd45b9294fbc604
Source dataset
uspto-grants-2003_08
Patent number
US06610707B1

Reaction notes

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