Hydrochloric Acid → HCID 88332345, compound

HRID 1941494Notes

Reaction equation

HRID 1941494 reaction equation
Cl.[NH2:2][OH:3].[F:4][C:5]([F:21])([F:20])[C:6]1[CH:11]=[CH:10][C:9]([CH:12]2[NH:17][C:16](=[O:18])[CH2:15][CH2:14][C:13]2=O)=[CH:8][CH:7]=1.Cl>N1C=CC=CC=1>[F:4][C:5]([F:21])([F:20])[C:6]1[CH:11]=[CH:10][C:9]([CH:12]2[NH:17][C:16](=[O:18])[CH2:15][CH2:14][C:13]2=[N:2][OH:3])=[CH:8][CH:7]=1

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 443297Hydroxyamine hydrochlorideHCID 22106595HCID 22106595, compound

Product 1

HCID 88332345HCID 88332345, compoundYield 61.1%

Reagents, catalysts & solvents 1

HCID 1049PyridineSolvent

Procedure

Pyridine (47 ml) and hydroxylamine hydrochloride (8.18 g) were added to a stirring solution of 6-(4-trifluoromethyl-phenyl)-piperidin-2,5-dione (5.04 g) under nitrogen. The mixture was heated at reflux for 21 h, cooled to room temperature, poured into aqueous hydrochloric acid (2M, 100 ml) and extracted with ethyl acetate (100 ml). The organic extract was washed with aqueous hydrochloric acid (3×100 ml) and the combined aqueous solution was extracted with ethyl acetate (2×50 ml). The combined organic solution was dried (MgSO4) and evaporated in vacuo to give the crude product (5.84 g) which was azeotroped with toluene (3×50 ml). FCC (dichloromethane: methanol, 12:1) gave the title compound (3.26 g) as an inseparable mixture of geometrical isomers (2:1). δ (d6 -DMSO) for the major isomer: 2.0-2.4 (m, 4H), 5.15 (d, 1H, J=3.5 Hz), 7.49 and 7.75 (2d, 4H, J=8 Hz for both). 8.39 (d, 1H, J=3.5 Hz), 11.08 (s, 1H). 1H-NMR signals for the minor isomer includes 5.77 (d, 1H, J=2.5 Hz), 7.59 and 7.72 (2d, 4H, J=8 Hz for both), 8.10 (d, 1H, J=2.5 Hz), 11.14 (s, 1H).

Workup

  1. temperatureThe mixture was heated
  2. temperatureat reflux for 21 h
  3. extractionextracted with ethyl acetate (100 ml)
  4. extractionThe organic extract
  5. washwas washed with aqueous hydrochloric acid (3×100 ml)
  6. extractionthe combined aqueous solution was extracted with ethyl acetate (2×50 ml)
  7. dry with materialThe combined organic solution was dried (MgSO4)
  8. customevaporated in vacuo
  9. customto give the crude product (5.84 g) which
  10. customwas azeotroped with toluene (3×50 ml)

Sources & evidence

ORD record
ord-35b9915062ac4937a4110dcc5c97f139
Source dataset
uspto-grants-1997_12
Patent number
US05703240

Reaction notes

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