Hydrochloric Acid → HCID 69737865, compound

HRID 896570Notes

Reaction equation

HRID 896570 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][CH2:9][N:10]2[C:15](=O)[CH2:14][C:13]([CH3:18])([CH3:17])[CH:12]([C:19]#[N:20])[C:11]2=O)=[CH:4][CH:3]=1.B.O1CCCC1.Cl>>[F:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][CH2:9][N:10]2[CH2:15][CH2:14][C:13]([CH3:18])([CH3:17])[CH:12]([CH2:19][NH2:20])[CH2:11]2)=[CH:4][CH:3]=1

Participants

5

Reactant 4

HCID 313Hydrochloric AcidHCID 6331BoraneHCID 8028TetrahydrofuranHCID 22350238HCID 22350238, compound

Product 1

HCID 69737865HCID 69737865, compoundYield 33%

Procedure

1-[2-(4-Fluorophenyl)-ethyl]-4,4-dimethyl-2,6-dioxopiperidine-3-carbonitrile (1.0 g, 3.47 mmol) was treated with 1.0 M borane in tetrahydrofuran (69.4 mL, 69.4 mmol) and stirred at room temperature for 18 hours. The solution was cooled on an ice bath and treated very slowly with 2.0 N hydrochloric acid. The mixture was concentrated under vacuum to remove the tetrahydrofuran, and the aqueous residue was heated at reflux for 60 minutes. The mixture was cooled to room temperature and treated with 50% aqueous sodium hydroxide to adjust the pH to about 11. The mixture was extracted with ethyl acetate, and the organic extracts were dried over sodium sulfate and concentrated. The residue was purified by flash chromatography, eluting with 10% methanol in dichloromethane, to provide an oil (300 mg, 33%). 1H NMR (300 MHz, CDCl3) δ7.15 (m, 2H), 6.96 (t, J=9 Hz, 2H), 3.66 (m, 1H), 3.11 (m, 2H), 2.97 (m, 1H), 2.9-2.7 (m, 3H), 2.60 (m, 2H), 2.39 (m, 1H), 2.24 (m, 1H), 2.00 (m, 1H), 1.7-1.3 (3H), 1.00 (s, 3H), 0.80 (s, 3H).

Workup

  1. temperatureThe solution was cooled on an ice bath
  2. concentrationThe mixture was concentrated under vacuum
  3. customto remove the tetrahydrofuran
  4. temperaturethe aqueous residue was heated
  5. temperatureat reflux for 60 minutes
  6. temperatureThe mixture was cooled to room temperature
  7. additiontreated with 50% aqueous sodium hydroxide
  8. extractionThe mixture was extracted with ethyl acetate
  9. dry with materialthe organic extracts were dried over sodium sulfate
  10. concentrationconcentrated
  11. customThe residue was purified by flash chromatography
  12. washeluting with 10% methanol in dichloromethane

Sources & evidence

ORD record
ord-73b8cb9b4e484f92a50eef106a89648e
Source dataset
uspto-grants-2005_07
Patent number
US06919356B2

Reaction notes

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