Sulfuric Acid → 4-(4-Oxopiperidin-1-yl)benzonitrile

HRID 1264323Notes

Reaction equation

HRID 1264323 reaction equation
O1[C:5]2([CH2:10][CH2:9][N:8]([C:11]3[CH:18]=[CH:17][C:14]([C:15]#[N:16])=[CH:13][CH:12]=3)[CH2:7][CH2:6]2)[O:4]CC1.OS(O)(=O)=O.CCOC(C)=O>C1COCC1.O>[O:4]=[C:5]1[CH2:6][CH2:7][N:8]([C:11]2[CH:18]=[CH:17][C:14]([C:15]#[N:16])=[CH:13][CH:12]=2)[CH2:9][CH2:10]1

Participants

6

Reactant 3

HCID 1118Sulfuric AcidHCID 8857Ethyl AcetateHCID 127174404-(1,4-Dioxa-8-azaspiro[4.5]decan-8-yl)benzonitrile

Product 1

HCID 110198874-(4-Oxopiperidin-1-yl)benzonitrileYield 84%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

To 4-(1,4-dioxa-8-aza-spiro[4.5]dec-8-yl)-benzonitrile (460 mg, 1.88 mmol, reference example 117) dissolved in THF (2 mL) was added 10% H2SO4 (4 mL) and the reaction was stirred for 24 h at room temperature. TLC (40% EtOAc in hexanes) shows a small amount of starting material, but mainly a more polar product. The reaction was diluted with water, extracted with dichloromethane (3×), washed with saturated aqueous NaCl solution, dried with Na2SO4, filtered and evaporated. The crude product was chromatographed on silica gel (20-40% EtOAc in hexanes) to afford the title compound (315 mg, 84%). 1H NMR (CDCl3): δ 7.52 (d, 2H), 6.88 (d, 2H), 3.72 (t, 4H), 2.57 (t, 4H). MS (ion spray) m/z 200 (M+).

Workup

  1. extractionextracted with dichloromethane (3×)
  2. washwashed with saturated aqueous NaCl solution
  3. dry with materialdried with Na2SO4
  4. filtrationfiltered
  5. customevaporated
  6. customThe crude product was chromatographed on silica gel (20-40% EtOAc in hexanes)

Sources & evidence

ORD record
ord-0bc943d7af5d4396b57a8b64b96b734e
Source dataset
uspto-grants-2003_04
Patent number
US06541505B1

Reaction notes

Loading…