Triethylamine → Tert-butyl 3,8-diazabicyclo[4.2.0]octane-3-carboxylate

HRID 1193049Notes

Reaction equation

HRID 1193049 reaction equation
C(O[C:4]([CH:6]1[CH2:11][CH2:10][N:9]([C:12]([O:14][C:15]([CH3:18])([CH3:17])[CH3:16])=[O:13])[CH2:8][C:7]1=O)=O)C.C(OC(C1CC[N:28](CC2C=CC=CC=2)CC1=O)=O)C.C(OC(OC(C)(C)C)=O)(OC(C)(C)C)=O.CCN(CC)CC>[OH-].[OH-].[Pd+2].CCO>[C:15]([O:14][C:12]([N:9]1[CH2:10][CH2:11][CH:6]2[CH:7]([NH:28][CH2:4]2)[CH2:8]1)=[O:13])([CH3:18])([CH3:17])[CH3:16]

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 90495Di-tert-butyl dicarbonateHCID 419705Ethyl 3-oxo-1-(phenylmethyl)-4-piperidinecarboxylateHCID 158529891-tert-Butyl 4-ethyl 3-oxopiperidine-1,4-dicarboxylate

Product 1

HCID 43810891Tert-butyl 3,8-diazabicyclo[4.2.0]octane-3-carboxylateYield 94.25%

Reagents, catalysts & solvents 2

HCID 9942167Palladium hydroxideCatalyst2×HCID 702EthanolSolvent

Procedure

3-Oxo-piperidine-1,4-dicarboxylic acid 1-tert-butyl ester 4-ethyl ester. A mixture of 1-benzyl-3-oxo-piperidine-4-carboxylic acid ethyl ester (11.31 g, 38 mmol), di-t-butyl dicarbonate (8.78 g, 40.2 mmol), Et3N (5.4 mL, 38.7 mmol) and Pd(OH)2 on carbon (20% on dry basis-Pearlman's catalyst) (1.3 g) were taken into EtOH (110 mL). The mixture was hydrogenated at 60 psi for 24 h in a Parr bottle. The catalyst was removed by filtration and the filtrate was concentrated to dryness to tan solid. Crude residue was shaken well with hexane (100 mL) and filtered. The filtrate was concentrated to yield the title compound (9.70 g, 94.25%). MS (ESI) mass calcd. for C13H21NO5, 271.32; 1H NMR (400 MHz, CDCl3) 4.24 (q, J=7.1, 2H), 4.03 (s br, 2H), 3.49 (t, J=5.6, 2H), 2.32 (m, 3H), 1.47 (s, 9H), 1.31 (t, J=7.1, 3H).

Workup

  1. customThe catalyst was removed by filtration
  2. concentrationthe filtrate was concentrated to dryness to tan solid
  3. filtrationfiltered
  4. concentrationThe filtrate was concentrated

Sources & evidence

ORD record
ord-25cf3afc30354182b238dc48eadbbf23
Source dataset
uspto-grants-2014_03
Patent number
US08680275B2

Reaction notes

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