Acetic Acid → 1-Cyclohexyl-4-methyl-pyrrolidin-2-one

HRID 2235180Notes

Reaction equation

HRID 2235180 reaction equation
[CH:1]1([N:7]2[CH2:11][CH:10]([CH2:12]O)[CH2:9][C:8]2=[O:14])[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.II.C(O)(=O)C>CN(C)C(=O)C.[Zn]>[CH:1]1([N:7]2[CH2:11][CH:10]([CH3:12])[CH2:9][C:8]2=[O:14])[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1

Participants

6

Reactant 3

HCID 176Acetic AcidHCID 807IodineHCID 242755161-Cyclohexyl-4-(hydroxymethyl)pyrrolidin-2-one

Product 1

HCID 134026541-Cyclohexyl-4-methyl-pyrrolidin-2-oneYield 45%

Reagents, catalysts & solvents 2

HCID 23994ZincCatalystHCID 31374DimethylacetamideSolvent2×

Conditions

Temperature
75 °C

Procedure

Place 1-cyclohexyl-4-hydroxymethyl-pyrrolidin-2-one (Preparation 2) (2.5 g, 12.7 mmol) and triphenylphosphene (3.7 g, 13.9 mmol) in a flask and add dry N,N-dimethyl-acetamide (20 mL). Add a solution of iodine (3.2 g, 12.7 mol) in N,N-dimethyl-acetamide (3 mL). Stir reaction for 24 hours. Quench the reaction with saturated sodium bisulfite (20 mL) and extract with methylene chloride. Dry over sodium sulfate, filter, and concentrate. Dissolve crude material in acetonitrile (100 mL) and add glacial acetic acid (15 mL) and zinc (12.4 g, 190.1 mmol), then heat to 75° C. and stir for 6 hours. Cool to room temperature, filter, and partition between water and methylene chloride. Separate layers and wash methylene chloride with saturated sodium bicarbonate. Dry over sodium sulfate, filter, and concentrate. Purify by silica gel (30-40% ethyl acetate in hexane) to yield 1.0 g (45%) of the title compound. NMR (CDCl3) δ 3.94 (m, 1H), 3.45 (m, 1H), 2.88 (dd, 1H), 2.55 (dd, 1H), 2.38 (m, 1H), 2.02 (dd, 1H), 1.78 (m, 2H), 1.68 (m, 3H), 1.35 (m, 4H), 1.09 (m, 4H).

Workup

  1. customreaction for 24 hours
  2. customQuench
  3. customthe reaction with saturated sodium bisulfite (20 mL)
  4. extractionextract with methylene chloride
  5. dry with materialDry over sodium sulfate
  6. filtrationfilter
  7. concentrationconcentrate
  8. dissolutionDissolve crude material in acetonitrile (100 mL)
  9. stirringstir for 6 hours
  10. temperatureCool to room temperature
  11. filtrationfilter
  12. custompartition between water and methylene chloride
  13. washSeparate layers and wash methylene chloride with saturated sodium bicarbonate
  14. dry with materialDry over sodium sulfate
  15. filtrationfilter
  16. concentrationconcentrate
  17. customPurify by silica gel (30-40% ethyl acetate in hexane)

Sources & evidence

ORD record
ord-cbaf3095f6e14c5da907cf631941228d
Source dataset
uspto-grants-2010_05
Patent number
US07713979B2

Reaction notes

Loading…