Sulfuric Acid → HCID 20692715, compound

HRID 379614Notes

Reaction equation

HRID 379614 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[N:9]=[C:10]([C:19]3([OH:26])[CH2:24][CH2:23][N:22]([CH3:25])[CH2:21][CH2:20]3)[NH:11][C:12]=2[C:13]2[CH:18]=[CH:17][N:16]=[CH:15][CH:14]=2)=[CH:4][CH:3]=1.OS(O)(=O)=O>C(O)CCC>[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[N:9]=[C:10]([C:19]3([O:26][CH2:7][CH2:2][CH2:3][CH3:4])[CH2:20][CH2:21][N:22]([CH3:25])[CH2:23][CH2:24]3)[NH:11][C:12]=2[C:13]2[CH:14]=[CH:15][N:16]=[CH:17][CH:18]=2)=[CH:4][CH:3]=1

Participants

4

Reactant 2

HCID 1118Sulfuric AcidHCID 10338084HCID 10338084, compound

Product 1

HCID 20692715HCID 20692715, compoundYield 120.5%

Reagents, catalysts & solvents 1

HCID 2631-ButanolSolvent

Conditions

Temperature
40 °C

Procedure

The product of example 12, 4-(4-Fluorophenyl)-5-(4-pyridyl) 2-(4-hydroxy-1-methylpiperidin-4-yl)imidazole (22.2 g; 63 mmol) is dissolved in 1-butanol (1 l) upon warming to 40° C. H2SO4 conc (27.8 g; 283 mmol) is added dropwise and the initially resulting suspension is refluxed for 3.5 h, while distilling off ˜200 ml of 1-butanol. The reaction mixture is cooled to room temperature and poured on a saturated solution of Na2CO3 (500 ml). The aqueous phase is extracted with ethyl acetate and the combined organic phases dried over Na2SO4, filtered and evaporated to dryness. Purification by chromatography (SiO2; TBME/MeOH/NH3conc. 96/4/0.4 to 70/30/1) yields the title compound as yellow crystals (15.5 g; 60.3%). A sample is recrystallized from CH2Cl2/TBME to render colorless crystals: m.p. 177° C.

Workup

  1. customthe initially resulting suspension
  2. temperatureis refluxed for 3.5 h
  3. distillationwhile distilling off ˜200 ml of 1-butanol
  4. temperatureThe reaction mixture is cooled to room temperature
  5. additionpoured on a saturated solution of Na2CO3 (500 ml)
  6. extractionThe aqueous phase is extracted with ethyl acetate
  7. dry with materialthe combined organic phases dried over Na2SO4
  8. filtrationfiltered
  9. customevaporated to dryness
  10. customPurification by chromatography (SiO2; TBME/MeOH/NH3conc. 96/4/0.4 to 70/30/1)

Sources & evidence

ORD record
ord-a495928857b94c46b566b251f65d61f9
Source dataset
uspto-grants-2001_10
Patent number
US06300347B1

Reaction notes

Loading…