Isopropanol → methyl (3S,4R)-4-(4-chlorophenyl)-2-oxopyrrolidine-3-carboxylate

HRID 2068159Notes

Reaction equation

HRID 2068159 reaction equation
CC(O)C.[Cl:5][C:6]1[CH:11]=[CH:10][C:9]([C@@H:12]([CH:17]([C:22]([O:24][CH3:25])=[O:23])[C:18](OC)=[O:19])[CH2:13][N+:14]([O-])=O)=[CH:8][CH:7]=1>[Fe].[Ni].O1CCCC1>[Cl:5][C:6]1[CH:11]=[CH:10][C:9]([C@@H:12]2[CH2:13][NH:14][C:18](=[O:19])[C@H:17]2[C:22]([O:24][CH3:25])=[O:23])=[CH:8][CH:7]=1

Participants

6

Reactant 2

HCID 3776IsopropanolHCID 11623829dimethyl (R)-2-(1-(4-chlorophenyl)-2-nitroethyl)malonate

Product 1

HCID 40541078methyl (3S,4R)-4-(4-chlorophenyl)-2-oxopyrrolidine-3-carboxylateYield 78.5%

Reagents, catalysts & solvents 3

HCID 935NickelCatalystHCID 23925IronCatalystHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
8 °C

Procedure

To 2-propanol (250 ml) was added dimethyl (R)-2-(1-(4-chlorophenyl)-2-nitroethyl)malonate (50.0 g, 158 mmol) and iron-containing developed nickel (5.0 g, containing iron 16.6%, aluminum 6.1%, manufactured by Kawaken Fine Chemical K.K.), and the mixture was reacted at 65° C. for 3 hours under a hydrogen pressure of 0.5 MPa (gauge pressure). After completion of the reaction, tetrahydrofuran (175 ml) was added, and the nickel catalyst was filtrated off. The nickel catalyst was washed with tetrahydrofuran (75 ml), and filtrate and washing liquid were combined, and acidic active alumina (5.0 g) was added to this and the mixture was thermally insulated at 50 to 60° C. The active alumina was filtrated off, then, the filtrate was concentrate under reduced pressure. The concentrated filtrate was cooled to 8° C., then, the resultant crystal was filtrated, and dried under reduced pressure, to obtain a title compound (31.4 g, 124 mmol) (yield: 78%). The spectrum data corresponded to the value in Example 2. The optical purity of the resultant compound was measured by HPLC to find a value of 99.73% ee. The content of a by-product obtained by releasing a chlorine atom was 0.06% (conditions are shown below).

Workup

  1. customthe mixture was reacted at 65° C. for 3 hours under a hydrogen pressure of 0.5 MPa (gauge pressure)
  2. additionwas added
  3. filtrationthe nickel catalyst was filtrated off
  4. washThe nickel catalyst was washed with tetrahydrofuran (75 ml), and filtrate
  5. washwashing liquid
  6. additionacidic active alumina (5.0 g) was added to this and the mixture
  7. customwas thermally insulated at 50 to 60° C
  8. filtrationThe active alumina was filtrated off
  9. concentrationthe filtrate was concentrate under reduced pressure
  10. filtrationthe resultant crystal was filtrated
  11. customdried under reduced pressure

Sources & evidence

ORD record
ord-370f26b9affe4ef0ad513a0becc65d65
Source dataset
uspto-grants-2012_10
Patent number
US08293926B2

Reaction notes

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