Hydrochloric Acid → 3-(2,6-Dichloro-4-methoxy-benzyl)-1-(4-oxo-cyclohexyl)-pyrrolidin-2-one

HRID 1013790Notes

Reaction equation

HRID 1013790 reaction equation
[Cl:1][C:2]1[CH:24]=[C:23]([O:25][CH3:26])[CH:22]=[C:21]([Cl:27])[C:3]=1[CH2:4][CH:5]1[CH2:9][CH2:8][N:7]([CH:10]2[CH2:19][CH2:18][C:13]3(OCC[O:14]3)[CH2:12][CH2:11]2)[C:6]1=[O:20].O.C1(C)C=CC(S(O)(=O)=O)=CC=1.Cl>CC(C)=O>[Cl:1][C:2]1[CH:24]=[C:23]([O:25][CH3:26])[CH:22]=[C:21]([Cl:27])[C:3]=1[CH2:4][CH:5]1[CH2:9][CH2:8][N:7]([CH:10]2[CH2:11][CH2:12][C:13](=[O:14])[CH2:18][CH2:19]2)[C:6]1=[O:20]

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 521998p-Toluenesulfonic acid monohydrateHCID 578785993-(2,6-Dichloro-4-methoxy-benzyl)-1-(1,4-dioxa-spiro[4.5]dec-8-yl)-pyrrolidin-2-one

Product 1

HCID 578786063-(2,6-Dichloro-4-methoxy-benzyl)-1-(4-oxo-cyclohexyl)-pyrrolidin-2-one

Reagents, catalysts & solvents 1

HCID 180AcetoneSolvent

Procedure

Dissolve 3-(2,6-Dichloro-4-methoxy-benzyl)-1-(1,4-dioxa-spiro[4.5]dec-8-yl)-pyrrolidin-2-one (6.5 g, 15.7 mmol) in acetone (100 mL), add p-toluenesulfonic acid hydrate (3 g, 15.7 mmol) and stir for 24 hr at room temp. Add 5N HCl (10 mL) and heat to 45° C. for 1 hr. Reaction progress can be monitored by TLC. Concentrate the reaction mixture, dilute with saturated aqueous sodium hydrogen carbonate (500 mL) and extract with ethyl acetate (3×150 mL). Wash the combined extracts with water (100 mL) and brine (100 mL), dry over anhydrous sodium sulfate, filtered, and concentrate to about 50 mL volume, dilute with hexanes (50 mL) and filter to give 5.5 g, 95%, as a white solid. 1H NMR (CDCl3) δ 6.78 (s, 2H), 4.44-4.52 (m, 1H), 3.78 (s, 3H), 3.37-3.47 (m, 1H), 3.29-3.36 (m, 1H), 3.15-3.23 (m, 2H), 2.39-2.62 (m, 4H), 1.80-2.11 (m, 6H). LCMS m+1 370.

Workup

  1. temperatureheat to 45° C. for 1 hr
  2. customReaction progress
  3. concentrationConcentrate the reaction mixture
  4. additiondilute with saturated aqueous sodium hydrogen carbonate (500 mL)
  5. extractionextract with ethyl acetate (3×150 mL)
  6. washWash the combined extracts with water (100 mL) and brine (100 mL)
  7. dry with materialdry over anhydrous sodium sulfate
  8. filtrationfiltered
  9. concentrationconcentrate to about 50 mL volume
  10. additiondilute with hexanes (50 mL)
  11. filtrationfilter
  12. customto give 5.5 g, 95%

Sources & evidence

ORD record
ord-cd2c0dce53404083b510070fd0e8c99f
Source dataset
uspto-grants-2011_07
Patent number
US07981918B2

Reaction notes

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