Dimethyl malonate → dimethyl (R)-2-(1-(4-chlorophenyl)-2-nitroethyl)malonate

HRID 2068155Notes

Reaction equation

HRID 2068155 reaction equation
[Cl:1][C:2]1[CH:12]=[CH:11][C:5]([CH:6]=[CH:7][N+:8]([O-:10])=[O:9])=[CH:4][CH:3]=1.[C:13]([O:20][CH3:21])(=[O:19])[CH2:14][C:15]([O:17][CH3:18])=[O:16]>C1(C)C=CC=CC=1.[Br-].C(N[C@H]1CCCC[C@@H]1NCC1C=CC=CC=1)C1C=CC=CC=1.C(N[C@H]1CCCC[C@@H]1NCC1C=CC=CC=1)C1C=CC=CC=1.[Ni+2].[Br-]>[Cl:1][C:2]1[CH:12]=[CH:11][C:5]([C@@H:6]([CH:14]([C:13]([O:20][CH3:21])=[O:19])[C:15]([O:17][CH3:18])=[O:16])[CH2:7][N+:8]([O-:10])=[O:9])=[CH:4][CH:3]=1

Participants

5

Reactant 2

HCID 7943Dimethyl malonateHCID 95339p-Chloro-beta-nitrostyrene

Product 1

HCID 11623829dimethyl (R)-2-(1-(4-chlorophenyl)-2-nitroethyl)malonateYield 75%

Reagents, catalysts & solvents 2

HCID 23582211nickel(II)bis[(S,S)-N,N'-dibenzylcyclohexane-1,2-diamine]bromideCatalystHCID 1140TolueneSolvent

Conditions

Temperature
50 °C

Procedure

This hydrated coarse crystal of 4-chloro-β-nitrostyrene was dissolved in toluene (19 ml), the aqueous phase was separated by a liquid-separation operation, and the organic phase was azeotropically dehydrated under reduced pressure, to distill off 9.5 ml. A catalyst prepared according to a method described in non-patent document 2 (nickel(II)bis[(S,S)—N,N′-dibenzylcyclohexane-1,2-diamine]bromide) (58 mg, 0.072 mmol) and dimethyl malonate (2.3 g, 17 mmol) were added, and the mixture was heated up to 50° C. and stirred at the same temperature for 7 hours. After completion of the reaction, the reaction solution was washed with 0.1 mol/L hydrochloric acid (5 ml) and water (5 ml) each once. The organic phase was concentrated under reduced pressure, and crystallized in a toluene/heptane solvent, to obtain 4.2 g (13 mmol) of a title compound. Yield 75%. The spectrum data corresponded to the value in non-patent document 3. The optical purity of the resultant title compound was measured by HPLC to find a value of 94% ee.

Workup

  1. customthe aqueous phase was separated by a liquid-separation operation
  2. distillationto distill off 9.5 ml
  3. customA catalyst prepared
  4. additionwere added
  5. customAfter completion of the reaction
  6. washthe reaction solution was washed with 0.1 mol/L hydrochloric acid (5 ml) and water (5 ml) each once
  7. concentrationThe organic phase was concentrated under reduced pressure
  8. customcrystallized in a toluene/heptane solvent

Sources & evidence

ORD record
ord-147a17d642f544a999582404ca4e844e
Source dataset
uspto-grants-2012_10
Patent number
US08293926B2

Reaction notes

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