Diisopropylethylamine → (S)-3-(4-(4-methoxybenzoyl)piperidin-1-yl)pyrrolidin-2-one

HRID 1752240Notes

Reaction equation

HRID 1752240 reaction equation
[CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([C:9]([CH:11]2[CH2:16][CH2:15][NH:14][CH2:13][CH2:12]2)=[O:10])=[CH:5][CH:4]=1.CS(O[C@@H:22]1[CH2:26][CH2:25][NH:24][C:23]1=[O:27])(=O)=O.CCN(C(C)C)C(C)C>C(#N)C.C(OCC)(=O)C>[CH3:1][O:2][C:3]1[CH:4]=[CH:5][C:6]([C:9]([CH:11]2[CH2:16][CH2:15][N:14]([C@H:22]3[CH2:26][CH2:25][NH:24][C:23]3=[O:27])[CH2:13][CH2:12]2)=[O:10])=[CH:7][CH:8]=1

Participants

6

Reactant 3

HCID 81531DiisopropylethylamineHCID 2740588(4-Methoxyphenyl)(piperidin-4-yl)methanoneHCID 89375789(R)-2-oxopyrrolidin-3-yl methanesulfonate

Product 1

HCID 71212280(S)-3-(4-(4-methoxybenzoyl)piperidin-1-yl)pyrrolidin-2-oneYield 59.1%

Reagents, catalysts & solvents 2

HCID 6342AcetonitrileSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a suspension of (4-methoxyphenyl)(piperidin-4-yl)methanone (34 g, 155 mmol) and (R)-2-oxopyrrolidin-3-yl methanesulfonate (34.7 g, 194 mmol) in acetonitrile (388 mL) at room temperature was added DIPEA (108 mL, 620 mmol) and the reaction was heated to 60 C for 29 h then allowed to cool to room temperature and stirred for an additional 24 h. The reaction mixture was concentrated in vacuo to afford a waxy solid which was taken up in ethyl acetate (300 mL) and sonicated. The mixture was filtered and the resulting white solid was washed with ethyl acetate (200 mL) to yield 21.05 g. The combined filtrates were concentrated and purified via silica gel chromatography (330 g isco 0.01% NH4OH 5-10% MeOH/ethyl acetate). Pure fractions were combined, concentrated in vacuo and then taken up in ethyl acetate (80-100 mL) and stirred. A white precipitate formed that was collected by filtration. The filtrate was concentrated to a gold oil, taken up in ethyl acetate to afford a white precipitate that was collected by filtration. A total of 27.7 g of the title material was obtained as a white solid. Calculated MS=302.4. found MS (ESI) m/e 303.4 (M+H+)

Workup

  1. temperaturethe reaction was heated to 60 C for 29 h
  2. concentrationThe reaction mixture was concentrated in vacuo
  3. customto afford a waxy solid which
  4. customsonicated
  5. filtrationThe mixture was filtered
  6. washthe resulting white solid was washed with ethyl acetate (200 mL)
  7. customto yield 21.05 g
  8. concentrationThe combined filtrates were concentrated
  9. custompurified via silica gel chromatography (330 g isco 0.01% NH4OH 5-10% MeOH/ethyl acetate)
  10. concentrationconcentrated in vacuo
  11. stirringstirred
  12. customA white precipitate formed
  13. filtrationthat was collected by filtration
  14. concentrationThe filtrate was concentrated to a gold oil
  15. customto afford a white precipitate that
  16. filtrationwas collected by filtration

Sources & evidence

ORD record
ord-49817b6c0273432e91eb3924e7fd2e1b
Source dataset
uspto-grants-2015_10
Patent number
US09163003B2

Reaction notes

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