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

HRID 1442911Notes

Reaction equation

HRID 1442911 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][C:11]([NH:17][C:18]([O:20][CH2:21][C:22]2[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=2)=[O:19])([C:14](O)=[O:15])[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].Cl.C[N:30](C)CCCN=C=NCC.ON1C2N=CC=CC=2N=N1.C(N(CC)CC)C.N>CN(C=O)C>[NH2:30][C:14]([C:11]1([NH:17][C:18]([O:20][CH2:21][C:22]2[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=2)=[O:19])[CH2:10][CH2:9][N:8]([C:6]([O:5][C:1]([CH3:3])([CH3:2])[CH3:4])=[O:7])[CH2:13][CH2:12]1)=[O:15]

Participants

7

Reactant 5

HCID 222AmmoniaHCID 8471TriethylamineHCID 181649HOAtHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 27566404-(((Benzyloxy)carbonyl)amino)-1-(tert-butoxycarbonyl)piperidine-4-carboxylic acid

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-benzyloxycarbonylamino-piperidine-1,4-dicarboxylic acid mono-tert-butyl ester (2.09 g, 5.52 mmol) in DMF (10 mL) was added 1-[3-(dimethylamino)propyl]-3-ethylcarbodiimide hydrochloride (1.27 g, 6.63 mmol), 1-hydroxy-7-azabenzotriazole (0.373 g, 2.76 mmol) and triethylamine (0.924 mL, 6.63 mmol), followed by ammonia (0.5 M in MeOH, 13.3 mL, 6.63 mmol). After 18 h the mixture was concentrated and the residue was partitioned between saturated aqueous NaHCO3 and ethyl acetate, the organic layer dried over MgSO4, and concentrated. The crude product was purified by silica gel chromatography, eluting with a gradient of 0 to 6% methanol:dichloromethane to give the title compound (0.43 g). MS: m/z=378.2 (M+1).

Workup

  1. concentrationAfter 18 h the mixture was concentrated
  2. customthe residue was partitioned between saturated aqueous NaHCO3 and ethyl acetate
  3. dry with materialthe organic layer dried over MgSO4
  4. concentrationconcentrated
  5. customThe crude product was purified by silica gel chromatography
  6. washeluting with a gradient of 0 to 6% methanol

Sources & evidence

ORD record
ord-b3d739627b154031914a68d48ad39104
Source dataset
uspto-grants-2010_02
Patent number
US07659264B2

Reaction notes

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