Ammonia → tert-Butyl 4-(((benzyloxy)carbonyl)amino)-4-carbamoylpiperidine-1-carboxylate

HRID 1664809Notes

Reaction equation

HRID 1664809 reaction equation
[CH2:1]([O:8][C:9]([NH:11][C:12]1([C:25]([OH:27])=O)[CH2:17][CH2:16][N:15]([C:18]([O:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[O:19])[CH2:14][CH2:13]1)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.Cl.C[N:30](C)CCCN=C=NCC.O.ON1C2C=CC=CC=2N=N1.C(N(CC)CC)C.N.C(=O)(O)[O-].[Na+]>CN(C)C=O>[NH2:30][C:25]([C:12]1([NH:11][C:9]([O:8][CH2:1][C:2]2[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=2)=[O:10])[CH2:17][CH2:16][N:15]([C:18]([O:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[O:19])[CH2:14][CH2:13]1)=[O:27]

Participants

8

Reactant 6

HCID 222AmmoniaHCID 8471TriethylamineHCID 516892Sodium BicarbonateHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 27566404-(((Benzyloxy)carbonyl)amino)-1-(tert-butoxycarbonyl)piperidine-4-carboxylic acidHCID 27960291-Hydroxybenzotriazole hydrate

Product 1

HCID 10714606tert-Butyl 4-(((benzyloxy)carbonyl)amino)-4-carbamoylpiperidine-1-carboxylateYield 20.6%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of 4-{[(benzyloxy)carbonyl]amino}-1-(tert-butoxycarbonyl)piperidine-4-carboxylic acid (2.09 g, 5.52 mmol) in N,N-dimethylformamide (10 mL) were added N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride (1.27 g, 6.63 mmol), 1-hydroxybenzotriazole hydrate (0.37 g, 2.76 mmol) and triethylamine (0.92 mL, 6.63 mmol), followed by ammonia (0.5 M in dioxane; 13.3 mL, 6.63 mmol). After 18 h, saturated aqueous sodium bicarbonate was added and the mixture was extracted with ethyl acetate. The combined organic extracts were dried over magnesium sulfate, filtered and concentrated. Purification by silica gel chromatography (100% dichloromethane→94% dichloromethane/methanol) to give the title compound (0.43 g). MS 378.2 (M+1).

Workup

  1. extractionthe mixture was extracted with ethyl acetate
  2. dry with materialThe combined organic extracts were dried over magnesium sulfate
  3. filtrationfiltered
  4. concentrationconcentrated
  5. customPurification by silica gel chromatography (100% dichloromethane→94% dichloromethane/methanol)

Sources & evidence

ORD record
ord-b4bc1a97e17c490bbdb15ee3403b7b41
Source dataset
uspto-grants-2011_10
Patent number
US08039460B2

Reaction notes

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