Benzyl chloroformate → 1-Boc-4-Cbz-amino-piperidine

HRID 1841935Notes

Reaction equation

HRID 1841935 reaction equation
C(N(C(C)C)CC)(C)C.[C:10]([O:14][C:15]([N:17]1[CH2:22][CH2:21][CH:20]([NH2:23])[CH2:19][CH2:18]1)=[O:16])([CH3:13])([CH3:12])[CH3:11].Cl[C:25]([O:27][CH2:28][C:29]1[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=1)=[O:26]>C1COCC1.C(OCC)(=O)C>[C:10]([O:14][C:15]([N:17]1[CH2:22][CH2:21][CH:20]([NH:23][C:25]([O:27][CH2:28][C:29]2[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=2)=[O:26])[CH2:19][CH2:18]1)=[O:16])([CH3:13])([CH3:11])[CH3:12]

Participants

6

Reactant 3

HCID 10387Benzyl chloroformateHCID 81531DiisopropylethylamineHCID 12682914-Amino-1-Boc-piperidine

Product 1

HCID 15143051-Boc-4-Cbz-amino-piperidineYield 73%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

Diisopropylethylamine (0.9 ml, 5.5 mmol) was added in one portion to a stirred solution of 4-amino-piperidine-1-carboxylic acid tert-butyl ester (1.0 g, 5.0 mmol) in THF (10 ml) at room temperature. To this mixture was added benzyl chloroformate (0.78 ml, 5.5 mmol) drop wise and the mixture was stirred at room temperature under a nitrogen atmosphere for 18 hours. After this time the mixture was diluted with ethyl acetate (50 ml) and washed with water (100 ml), saturated NaHCO3 (100 ml) and HCl (100 ml, 2M). The organic layer was separated, dried (MgSO4), filtered and concentrated under vacuum. The resulting residue was purified by flash column chromatography (elution: 50% heptane, 50% ethyl acetate) to give the title compound (1.2 g, 73% yield) as a colourless oil. Tr=2.08 min m/z (ES+) (M+Na+) 357.

Workup

  1. washwashed with water (100 ml), saturated NaHCO3 (100 ml) and HCl (100 ml, 2M)
  2. customThe organic layer was separated
  3. dry with materialdried (MgSO4)
  4. filtrationfiltered
  5. concentrationconcentrated under vacuum
  6. customThe resulting residue was purified by flash column chromatography (elution: 50% heptane, 50% ethyl acetate)

Sources & evidence

ORD record
ord-d41eef6a917741eb8ff62e0483723853
Source dataset
uspto-grants-2015_02
Patent number
US08946197B2

Reaction notes

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