Ethylbenzene → 3-(2-Nitro-1-pyridin-3-yl-ethyl)-piperidine-1,3-dicarboxylic acid 1-tert-butyl ester 3-ethyl ester

HRID 1036720Notes

Reaction equation

HRID 1036720 reaction equation
[CH2:1]([O:3][C:4]([CH:6]1[CH2:11][CH2:10][CH2:9][N:8]([C:12]([O:14][C:15]([CH3:18])([CH3:17])[CH3:16])=[O:13])[CH2:7]1)=[O:5])[CH3:2].[Li+].CC([N-]C(C)C)C.C(C1C=CC=CC=1)C.[N+:35]([CH:38]=[CH:39][C:40]1[CH:41]=[N:42][CH:43]=[CH:44][CH:45]=1)([O-:37])=[O:36]>C1COCC1.CCCCCCC.CN(C=O)C>[CH2:1]([O:3][C:4]([C:6]1([CH:39]([C:40]2[CH:41]=[N:42][CH:43]=[CH:44][CH:45]=2)[CH2:38][N+:35]([O-:37])=[O:36])[CH2:11][CH2:10][CH2:9][N:8]([C:12]([O:14][C:15]([CH3:17])([CH3:16])[CH3:18])=[O:13])[CH2:7]1)=[O:5])[CH3:2]

Participants

8

Reactant 4

HCID 7500EthylbenzeneHCID 3577271-Tert-butyl 3-ethyl piperidine-1,3-dicarboxylateHCID 591283Pyridine, 3-(2-nitroethenyl)-HCID 2724682Lithium diisopropylamide

Product 1

HCID 710602643-(2-Nitro-1-pyridin-3-yl-ethyl)-piperidine-1,3-dicarboxylic acid 1-tert-butyl ester 3-ethyl ester

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolvent2×HCID 8900HeptaneSolvent

Conditions

Temperature
-40 °C

Procedure

To a cooled (−78° C.) solution of ethyl-1-BOC-3-piperidinecarboxylate (1.53 g, 10.20 mmol) in THF (15 ml) was added dropwise 2M LDA in heptane, THF, and ethylbenzene (5.34 ml, 10.69 mmol) and the resulting mixture was allowed to warm to −40° C. over 1 h and then cooled back to −78° C. A solution of 3-(2-nitroethenyl)pyridine (1.53 g, 10.20 mmol) in DMF (5 ml) was added dropwise and the reaction mixture was allowed to warm to RT over 1 h. The reaction was quenched with NH4Cl saturated aqueous solution (50 ml) and extracted with EtOAc (200 ml). The combined organic extracts were dried (MgSO4) and concentrated in vacuo. Purification of the crude product by chromatography on silica eluting with 0-10% MeOH in DCM afforded the title compounds as a yellow oil.

Workup

  1. temperaturecooled back to −78° C
  2. temperatureto warm to RT over 1 h
  3. customThe reaction was quenched with NH4Cl saturated aqueous solution (50 ml)
  4. extractionextracted with EtOAc (200 ml)
  5. dry with materialThe combined organic extracts were dried (MgSO4)
  6. concentrationconcentrated in vacuo
  7. customPurification of the crude product by chromatography on silica eluting with 0-10% MeOH in DCM

Sources & evidence

ORD record
ord-fd5ee8726a674e69a49fe435b18af0c3
Source dataset
uspto-grants-2013_10
Patent number
US08546416B2

Reaction notes

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