Hydrochloric Acid → tert-Butyl cis(+/-)-4-{[(4-chloro-5-ethyl-1H-imidazol-2-yl)carbonyl]amino}-3-methoxypiperidine-1-carboxylate

HRID 43433Notes

Reaction equation

HRID 43433 reaction equation
CCN=C=NCCCN(C)C.Cl.[NH2:13][C@H:14]1[CH2:19][CH2:18][N:17]([C:20]([O:22][C:23]([CH3:26])([CH3:25])[CH3:24])=[O:21])[CH2:16][C@H:15]1[O:27][CH3:28].[Cl:29][C:30]1[N:31]=[C:32]([C:37](OCC)=[O:38])[NH:33][C:34]=1[CH2:35][CH3:36].Cl>CN(C1C=CN=CC=1)C.CC(N(C)C)=O>[Cl:29][C:30]1[N:31]=[C:32]([C:37]([NH:13][C@H:14]2[CH2:19][CH2:18][N:17]([C:20]([O:22][C:23]([CH3:24])([CH3:25])[CH3:26])=[O:21])[CH2:16][C@H:15]2[O:27][CH3:28])=[O:38])[NH:33][C:34]=1[CH2:35][CH3:36]

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 57362389(3R,4S)-4-Amino-1-boc-3-methoxypiperidineHCID 67549841ethyl 4-chloro-5-ethyl-1H-imidazole-2-carboxylate

Product 1

HCID 86648452tert-Butyl cis(+/-)-4-{[(4-chloro-5-ethyl-1H-imidazol-2-yl)carbonyl]amino}-3-methoxypiperidine-1-carboxylateYield 62%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 31374DimethylacetamideSolvent

Procedure

WSC hydrochloride (580 mg, 3.02 mmol) and DMAP (125 mg, 1.02 mmol) were added to a solution of tert-butyl cis(±)-4-amino-3-methoxypiperidine-1-carboxylate obtained in Example (1e) (230 mg, 0.99 mmol) and ethyl 4-chloro-5-ethyl-1H-imidazole-2-carboxylate obtained in Example (1d) (85 mg, 0.49 mmol) in DMA (5 mL), and the mixture was stirred at room temperature for three hours. Dilute hydrochloric acid was added to the reaction solution, followed by extraction with ethyl acetate. Then, the organic layer was washed with water, saturated aqueous sodium bicarbonate solution and brine, and dried over anhydrous sodium sulfate. Following concentration under reduced pressure, the residue was purified by silica gel column chromatography (elution solvent: hexane/ethyl acetate=1/1, ethyl acetate) to obtain 117 mg of the title compound as a pale yellow solid (62%).

Workup

  1. extractionfollowed by extraction with ethyl acetate
  2. washThen, the organic layer was washed with water, saturated aqueous sodium bicarbonate solution and brine
  3. dry with materialdried over anhydrous sodium sulfate
  4. concentrationconcentration under reduced pressure
  5. customthe residue was purified by silica gel column chromatography (elution solvent: hexane/ethyl acetate=1/1, ethyl acetate)

Sources & evidence

ORD record
ord-564bb2056dac433a9fccbd386cf7da00
Source dataset
uspto-grants-2013_09
Patent number
US08536197B2

Reaction notes

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