Sodium Hydroxide → 4-(4-Fluorophenyl)-2-Bromo-1-(3-Phenylpropyl)-5-(4-Pyridyl)-Imidazole

HRID 719755Notes

Reaction equation

HRID 719755 reaction equation
[C:1]1([CH2:7][CH2:8][CH2:9][N:10]2[C:14]([C:15]3[CH:20]=[CH:19][N:18]=[CH:17][CH:16]=3)=[C:13]([C:21]3[CH:26]=[CH:25][C:24]([F:27])=[CH:23][CH:22]=3)[NH:12][C:11]2=O)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.P(Br)(Br)([Br:31])=O.S1(CCCC1)(=O)=O.[OH-].[Na+]>>[F:27][C:24]1[CH:25]=[CH:26][C:21]([C:13]2[N:12]=[C:11]([Br:31])[N:10]([CH2:9][CH2:8][CH2:7][C:1]3[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=3)[C:14]=2[C:15]2[CH:20]=[CH:19][N:18]=[CH:17][CH:16]=2)=[CH:22][CH:23]=1

Participants

5

Reactant 4

HCID 14798Sodium Hydroxide3×HCID 24613Phosphorus oxybromideHCID 31347SulfolaneHCID 113262601,3-Dihydro-1-(3-phenylpropyl)-4-(4-fluorophenyl)-5-(4-pyridyl)-imidazol-2-one

Product 1

HCID 113395554-(4-Fluorophenyl)-2-Bromo-1-(3-Phenylpropyl)-5-(4-Pyridyl)-Imidazole

Conditions

Temperature
40 °C

Procedure

1,3-Dihydro-1-(3-phenylpropyl)-4-(4-fluorophenyl)-5-(4-pyridyl)-2H-imidazol-2-one (100 g, 0.26 mol) was mixed with POBr3 (268.7 g, 0.93 mol) and sulfolane (200 g) and the reaction mixture was heated to a temperature of 120–125° C. for 1–2 h. Upon completion, the reaction mixture was cooled to 40° C. Cautiously, over about 30 min, 2N NaOH solution (53 g) was added. Additional 2N NaOH solution (53 g) was then added at faster rate. The reaction mixture was then cooled to 15–20° C. and 4N NaOH solution (802 g) was added to adjust the solution to pH 7–8. The aqueous phase was extracted with t-butylmethyl ether (3×143 g) and the organic phases combined. To the combined organic phase was added t-butylmethyl ether (107 g). The solution was washed with water (2×150 g), resulting in the precipitation of a solid, which was collected by filtration.

Workup

  1. temperaturethe reaction mixture was heated to a temperature of 120–125° C. for 1–2 h
  2. temperatureThe reaction mixture was then cooled to 15–20° C.
  3. extractionThe aqueous phase was extracted with t-butylmethyl ether (3×143 g)
  4. additionTo the combined organic phase was added t-butylmethyl ether (107 g)
  5. washThe solution was washed with water (2×150 g)
  6. customresulting in the precipitation of a solid, which
  7. filtrationwas collected by filtration

Sources & evidence

ORD record
ord-80f87efb730c491abfcd7a5186465444
Source dataset
uspto-grants-2006_11
Patent number
US07132544B2

Reaction notes

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