Sulfuric Acid → (5R)-5-([1,1′-Biphenyl]-4-ylmethyl)-2-pyrrolidinone

HRID 882508Notes

Reaction equation

HRID 882508 reaction equation
[C:1]1([C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=2)[CH:6]=[CH:5][C:4]([C:7]([C@@H:9]2[NH:13][C:12](=[O:14])[CH2:11][CH2:10]2)=O)=[CH:3][CH:2]=1.S(=O)(=O)(O)O>O1CCCC1>[C:1]1([C:15]2[CH:16]=[CH:17][CH:18]=[CH:19][CH:20]=2)[CH:2]=[CH:3][C:4]([CH2:7][C@@H:9]2[NH:13][C:12](=[O:14])[CH2:11][CH2:10]2)=[CH:5][CH:6]=1

Participants

4

Reactant 2

HCID 1118Sulfuric AcidHCID 66739256HCID 66739256, compound

Product 1

HCID 66739157(5R)-5-([1,1′-Biphenyl]-4-ylmethyl)-2-pyrrolidinone

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
30 °C

Procedure

14 g of (R)-5-(biphenyl-4-carbonyl)pyrrolidin-2-one are suspended in 80 ml tetrahydrofuran. Subsequently 331 mg of concentrated sulphuric acid are added and the reaction vessel is purged with argon. 1.4 g of palladium on carbon 10% m/m (W. C. Heraeus GmbH, Type K-0218) is added and the mixture is stirred under an atmosphere of hydrogen (3 bar) at 30° C. for 20 h. The black suspension is filtered and the filter cake is washed with tetrahydrofuran. After the addition of 50 ml water, the pH of the emulsion is adjusted to pH 5.5 using sodium hydroxide solution (2M). Under reduced pressure, the organic solvent is removed and 100 ml of isopropyl acetate are added. The aqueous layer is then separated and the remaining organic layer is concentrated to approx. half of its original volume. The suspension is cooled to −5° C. and filtered. The filter cake is washed with cooled isopropyl acetate and is dried under reduced pressure to give (R)-5-biphenyl-4-ylmethylpyrrolidin-2-one as colourless crystals. 1H-NMR (CDCl3): 1.93 (1H); 2.37 (3H); 2.80 (1H, dd, J=8.5, 13.5); 2.92 (1H, dd, J=5.4, 13.5); 3.95 (1H); 5.70 (1H); 7.29 (1H, d, J=7.5); 7.38 (1H); 7.47 (2H); 7.59 (4H). MS (ESI, m/e) 252 [M+H]+; 503 [2M+H]+. IR (solution in CH2Cl2, /cm−1): 3191; 3055; 2930; 1692; 1489; 1272; 762; 692.

Workup

  1. customthe reaction vessel is purged with argon
  2. addition1.4 g of palladium on carbon 10% m/m (W. C. Heraeus GmbH, Type K-0218) is added
  3. filtrationThe black suspension is filtered
  4. washthe filter cake is washed with tetrahydrofuran
  5. additionAfter the addition of 50 ml water
  6. customUnder reduced pressure, the organic solvent is removed
  7. addition100 ml of isopropyl acetate are added
  8. customThe aqueous layer is then separated
  9. concentrationthe remaining organic layer is concentrated to approx. half of its original volume
  10. temperatureThe suspension is cooled to −5° C.
  11. filtrationfiltered
  12. washThe filter cake is washed with cooled isopropyl acetate
  13. customis dried under reduced pressure

Sources & evidence

ORD record
ord-3414e1a2039f4346a65c8d92d8103fdd
Source dataset
uspto-grants-2015_03
Patent number
US08993785B2

Reaction notes

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