Hydrochloric Acid → HCID 131734545, compound

HRID 592095Notes

Reaction equation

HRID 592095 reaction equation
[K].[CH3:2][O:3][CH2:4][C:5]([CH:7]1[CH2:11][CH2:10][N:9]([C:12]([O:14][C:15]([CH3:18])([CH3:17])[CH3:16])=[O:13])[C:8]1=[O:19])=O.Cl.[NH2:21][C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1.O.C1(C)C=CC(S(O)(=O)=O)=CC=1>C1CCCCC1.C1(C)C=CC=CC=1>[CH3:2][O:3][CH2:4][C:5](=[C:7]1[CH2:11][CH2:10][N:9]([C:12]([O:14][C:15]([CH3:18])([CH3:17])[CH3:16])=[O:13])[C:8]1=[O:19])[NH:21][C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 6115AnilineHCID 521998p-Toluenesulfonic acid monohydrateHCID 117841197HCID 117841197, compound

Product 1

HCID 131734545HCID 131734545, compoundYield 34.3%

Reagents, catalysts & solvents 2

HCID 1140TolueneSolventHCID 8078CyclohexaneSolvent

Procedure

Into a 200 mL four-mouthed flask were added tert-butyl 3-(2-methoxyacetyl)-2-oxopyrrolidine-1-carboxylate potassium salt (9.00 g) [mw. 295.37, 30.47 mmol], 1 mol/L aqueous hydrochloric acid solution (50 mL) and toluene (90 mL), and the mixture was stirred at room temperature for 10 min. After partitioning, the organic layer was washed with water (50 mL), and dried over magnesium sulfate. After filtration, aniline (2.84 g) [mw. 93.13, 30.50 mmol], p-toluenesulfonic acid monohydrate (0.58 g) [mw. 190.22, 3.05 mmol] and cyclohexane (50 mL) were added. Dean-Stark trap was set, and distillation by thermal dehydration was performed for 1 hr. After cooling to room temperature, 5 w/w % aqueous acetic acid solution (50 mL) was added to allow for partitioning. The organic layer was washed successively with 5 w/w % aqueous sodium bicarbonate solution (50 mL) and water (50 mL), further washed with water (50 mL), dried over magnesium sulfate, filtered and concentrated under reduced pressure. To the concentrate were added methanol (78 mL) and activated carbon (0.78 g), and the mixture was stirred at room temperature for 1 hr. After filtration, the mother liquor was concentrated under reduced pressure, and the solvent was replaced with ethyl acetate. To the concentrate was added diisopropyl ether (22 mL) to allow for crystallization, and the crystals were aged for 1 hr. After filtration under reduced pressure, the crystals were washed with diisopropyl ether (8 mL), and dried at 40° C. under reduced pressure to give the object compound. Pale-yellow crystals, 3.47 g, yield 34.3%, 1H-NMR (500 MHz, DMSO-d6, TMS) δ 1.47 (s, 9H), 2.70 (t, J=7.7 Hz, 2H), 3.26 (s, 3H), 3.65 (t, J=8.1 Hz, 2H), 4.06 (s, 2H), 7.07-7.14 (m, 3H), 7.31-7.35 (m, 2H), 10.34 (s, 1H). 13C-NMR (125 MHz, DMSO-d6) δ 20.29, 27.74, 43.23, 57.83, 67.40, 89.97, 100.10, 121.40, 123.48, 129.20, 139.43, 148.97, 150.33, 169.16. MS (ESI) m/z 333.1776 [M+H]+, 355.1629 [M+Na]+, 331.1672 [M−H]−. Found: C, 65.04; H, 7.28; N, 8.43%. Calcd for C18H24N2O4: C, 64.97; H, 7.20; N, 8.37%.

Workup

  1. customAfter partitioning
  2. washthe organic layer was washed with water (50 mL)
  3. dry with materialdried over magnesium sulfate
  4. additionwere added
  5. distillationdistillation by thermal dehydration
  6. waitwas performed for 1 hr
  7. temperatureAfter cooling to room temperature
  8. additionwas added
  9. customfor partitioning
  10. washThe organic layer was washed successively with 5 w/w % aqueous sodium bicarbonate solution (50 mL) and water (50 mL)
  11. washfurther washed with water (50 mL)
  12. dry with materialdried over magnesium sulfate
  13. filtrationfiltered
  14. concentrationconcentrated under reduced pressure
  15. additionTo the concentrate were added methanol (78 mL) and activated carbon (0.78 g)
  16. stirringthe mixture was stirred at room temperature for 1 hr
  17. filtrationAfter filtration
  18. concentrationthe mother liquor was concentrated under reduced pressure
  19. additionTo the concentrate was added diisopropyl ether (22 mL)
  20. customto allow for crystallization
  21. waitthe crystals were aged for 1 hr
  22. filtrationAfter filtration under reduced pressure
  23. washthe crystals were washed with diisopropyl ether (8 mL)
  24. customdried at 40° C. under reduced pressure
  25. customto give the object compound

Sources & evidence

ORD record
ord-6c1d150b61da41ffa9eb448d6685a598
Source dataset
uspto-grants-2016_01
Patent number
US09238667B2

Reaction notes

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