Hydrochloric Acid → 6-[2-(4-Piperidyl)ethyl]spiro[[1,3]dioxolo[4,5-f]isoindole-7,1'-cyclopropane]-5-one hydrochloride

HRID 528510Notes

Reaction equation

HRID 528510 reaction equation
[O:1]=[C:2]1[C:12]2[CH:11]=[C:10]3[O:13][CH2:14][O:15][C:9]3=[CH:8][C:7]=2[C:4]2([CH2:6][CH2:5]2)[N:3]1[CH2:16][CH2:17][CH:18]1[CH2:23][CH2:22][N:21](C(OC(C)(C)C)=O)[CH2:20][CH2:19]1.[ClH:31]>C(O)C>[ClH:31].[NH:21]1[CH2:22][CH2:23][CH:18]([CH2:17][CH2:16][N:3]2[C:4]3([CH2:6][CH2:5]3)[C:7]3[CH:8]=[C:9]4[O:15][CH2:14][O:13][C:10]4=[CH:11][C:12]=3[C:2]2=[O:1])[CH2:19][CH2:20]1

Participants

4

Reactant 2

HCID 313Hydrochloric AcidHCID 90064497Tert-butyl 4-[2-(5-oxospiro[[1,3]dioxolo[4,5-f]isoindole-7,1'-cyclopropane]-6-yl)ethyl]piperidine-1-carboxylate

Product 1

HCID 1180573846-[2-(4-Piperidyl)ethyl]spiro[[1,3]dioxolo[4,5-f]isoindole-7,1'-cyclopropane]-5-one hydrochlorideYield 46.2%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

To a reaction vessel, all compound XV obtained in the above step and 750 ml ethanol were added. The mixture was heated until dissolved completely, 36 ml concentrated hydrochloric acid was added, the reaction was kept at about 50-55° C. for 5 h, concentrated to about 200 ml under reduced pressure, 900 ml ethyl acetate was added dropwise, cooled and filtered, the filter cake was washed and dried, and 24.3 g compound II-5 was obtained, with yield of 46.2% (calculated according to compound IX-1). 1H NMR (D2O): δ 1.06 (t, 2H, J=6.7 Hz), 1.32-1.46 (m, 6H), 1.60 (m, 1H), 1.91 (d, 2H, J=13.5 Hz), 2.91-3.03 (m, 4H), 3.39 (d, 2H, J=12.8 Hz), 5.90 (s, 2H), 6.18 (s, 1H), 6.68 (s, 1H); MS (ESI): m/z 315 [M-Cl]+.

Workup

  1. additionwere added
  2. temperatureThe mixture was heated
  3. dissolutionuntil dissolved completely
  4. concentrationconcentrated to about 200 ml under reduced pressure, 900 ml ethyl acetate
  5. additionwas added dropwise
  6. temperaturecooled
  7. filtrationfiltered
  8. washthe filter cake was washed
  9. customdried
  10. customwas obtained, with yield of 46.2% (calculated according to compound IX-1)

Sources & evidence

ORD record
ord-17498c682d67441ca9374c8bf2c93791
Source dataset
uspto-grants-2016_05
Patent number
US09346818B2

Reaction notes

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