Hydrochloric Acid → HCID 22615492, compound

HRID 842726Notes

Reaction equation

HRID 842726 reaction equation
[CH3:1][N:2]1[CH2:7][CH2:6][C:5]2([C:15]3[C:10](=[C:11]4[O:19][CH2:18][CH2:17][O:16][C:12]4=[CH:13][CH:14]=3)[C:9](=O)[O:8]2)[CH2:4][CH2:3]1.O1CCCC1.B.Cl>O1CCCC1>[CH3:1][N:2]1[CH2:7][CH2:6][C:5]2([C:15]3[C:10](=[C:11]4[O:19][CH2:18][CH2:17][O:16][C:12]4=[CH:13][CH:14]=3)[CH2:9][O:8]2)[CH2:4][CH2:3]1

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 2723981Borane;tetrahydrofuranHCID 22615486HCID 22615486, compound

Product 1

HCID 22615492HCID 22615492, compoundYield 70.3%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

Into a 100 ml round bottom flask fitted with a nitrogen inlet, condenser, and magnetic stirring bar containing 10.9 ml of anhydrous tetrahydrofuran at 0° was placed 1′-methyl-(4,5-ethylendioxy)spiro(isobenzofuran-1(3H),4′-piperidin)-3-one (1.124 g, 4.08 mmol). Borane tetrahydrofuran complex (1.0 M in tetrahydrofuran, 10.2 mmol) was added slowly via syringe. The mixture was heated to reflux for 72 hours and then cooled to 0°. 5N hydrochloric acid (4 ml) was then added via syringe before heating the mixture to reflux again for 5 hours. The solution was then concentrated in vacuo and partitioned between ethyl acetate and water. The aqueous layer was made basic with concentrated ammonium hydroxide and sodium chloride was added past point of saturation. The aqueous layer was extracted again with ethyl acetate (three times) and the combined organics were dried over sodium sulfate, filtered, and concentrated. The residue was taken up in 2% methanol:ammonium hydroxide and chromatographed (100:10:1 methylene chloride:methanol:ammonium hydroxide) to give 750 mg of subtitled product (70%) which was used directly in the next step.

Workup

  1. customInto a 100 ml round bottom flask fitted with a nitrogen inlet, condenser, and magnetic stirring bar
  2. temperatureThe mixture was heated
  3. temperatureto reflux for 72 hours
  4. temperaturecooled to 0°
  5. temperaturebefore heating the mixture
  6. temperatureto reflux again for 5 hours
  7. concentrationThe solution was then concentrated in vacuo
  8. custompartitioned between ethyl acetate and water
  9. additionwas added past point of saturation
  10. extractionThe aqueous layer was extracted again with ethyl acetate (three times)
  11. dry with materialthe combined organics were dried over sodium sulfate
  12. filtrationfiltered
  13. concentrationconcentrated
  14. customammonium hydroxide and chromatographed (100:10:1 methylene chloride:methanol:ammonium hydroxide)

Sources & evidence

ORD record
ord-a8187cf9116b4a0986de8efd8a7e2cc6
Source dataset
uspto-grants-2002_04
Patent number
US06376505B1

Reaction notes

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