Sulfuric Acid → 5-([1,1'-Biphenyl]-4-ylmethyl)pyrrolidin-2-one

HRID 1641631Notes

Reaction equation

HRID 1641631 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]([CH:9]2[NH:13][C:12](=[O:14])[CH2:11][CH2:10]2)=O)=[CH:3][CH:2]=1.OS(O)(=O)=O.[H][H]>C1COCC1.CO.C1(C)C=CC=CC=1.[Pd]>[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][CH:9]2[NH:13][C:12](=[O:14])[CH2:11][CH2:10]2)=[CH:5][CH:6]=1

Participants

8

Reactant 3

HCID 1118Sulfuric AcidHCID 17772957(r/s)-5-(Biphenyl-4-carbonyl)pyrrolidin-2-oneHCID 178418361HCID 178418361, compound

Product 1

HCID 593184595-([1,1'-Biphenyl]-4-ylmethyl)pyrrolidin-2-oneYield 96.5%

Reagents, catalysts & solvents 4

HCID 23938PalladiumCatalystHCID 887MethanolSolventHCID 1140TolueneSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
50 °C

Procedure

A mixture of 26.5 g (100 mmol) (R/S)-5-(biphenyl-4-carbonyl)pyrrolidin-2-one, 3.0 g Pd/C (10% PD CP 4505 D/R Catalyst, BASF), 5 g conc. H2SO4 in 300 ml THF and 300 ml MeOH are hydrogenated at 1 atm pressure and heated at 50° C. After 10 h the hydrogen uptake stops. The catalyst is filtered off, washed with methanol and the resulting filtrate is concentrated in vacuo. The evaporation residue is dissolved in toluene and is washed with aqueous Na2CO3 solution. A part of the product precipitates and is filtered and dried in vacuo (96.5% HPLC area %). The toluene phase is washed twice with H2O and evaporated completely, to yield further crude product. This further crude product is purified over silica gel chromatography with toluene/methanol=4:1, to yield the product. This product is stirred in 70 ml toluene at 60° C. for 2 h. Then 70 ml heptanes fraction are added and the precipitate is filtered. The precipitate is dried in vacuo to yield (R/S)-5-biphenyl-4-ylmethylpyrrolidin-2-one (96.5% HPLC area %). 1H NMR (DMSO): 1.69 (1H), 1.96-2.05 (2H), 2.67 (1H), 2.84 (1H), 3.80 (1H), 7.31 (2H), 7.44 (2H), 7.57 (2H), 7.63 (2H), 7.74 (1H).

Workup

  1. filtrationThe catalyst is filtered off
  2. washwashed with methanol
  3. concentrationthe resulting filtrate is concentrated in vacuo
  4. dissolutionThe evaporation residue is dissolved in toluene
  5. washis washed with aqueous Na2CO3 solution
  6. customA part of the product precipitates
  7. filtrationis filtered
  8. customdried in vacuo (96.5% HPLC area %)
  9. washThe toluene phase is washed twice with H2O
  10. customevaporated completely
  11. customto yield further crude product
  12. customThis further crude product is purified over silica gel chromatography with toluene/methanol=4:1
  13. customto yield the product
  14. filtrationthe precipitate is filtered
  15. customThe precipitate is dried in vacuo

Sources & evidence

ORD record
ord-b2dcd3a5b05e40fd9786a5c4392af02c
Source dataset
uspto-grants-2012_02
Patent number
US08115016B2

Reaction notes

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