Iodine → HCID 21258211, compound

HRID 635212Notes

Reaction equation

HRID 635212 reaction equation
Br[C:2]1[CH:3]=[C:4]([Cl:8])[CH:5]=[CH:6][CH:7]=1.[Mg].II.[Br:12][C:13]1[CH:18]=[C:17]([CH:19]([CH3:21])[CH3:20])[CH:16]=[CH:15][C:14]=1[N:22]([C:25]1[N:30]=[C:29]([N:31]2[CH2:36][CH2:35][C:34](=[O:37])[CH2:33][CH2:32]2)[CH:28]=[C:27]([CH3:38])[N:26]=1)[CH2:23][CH3:24].[Cl-].[NH4+]>O1CCCC1>[Br:12][C:13]1[CH:18]=[C:17]([CH:19]([CH3:20])[CH3:21])[CH:16]=[CH:15][C:14]=1[N:22]([C:25]1[N:30]=[C:29]([N:31]2[CH2:36][CH2:35][C:34]([C:2]3[CH:7]=[CH:6][CH:5]=[C:4]([Cl:8])[CH:3]=3)([OH:37])[CH2:33][CH2:32]2)[CH:28]=[C:27]([CH3:38])[N:26]=1)[CH2:23][CH3:24]

Participants

7

Reactant 5

HCID 807IodineHCID 79281-Bromo-3-chlorobenzeneHCID 25517Ammonium ChlorideHCID 5462224MagnesiumHCID 21258201HCID 21258201, compound

Product 1

HCID 21258211HCID 21258211, compoundYield 58.8%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

3-Bromochlorobenzene (427 mg), 27 mg of magnesium, and a trace amount of iodine were heated in 5 ml of tetrahydrofuran under reflux for 1 hour. The reaction mixture was cooled with ice and added dropwise to a solution of 321 mg of 2-[N-(2-bromo-4-isopropylphenyl)-N-ethylamino]-6-methyl-4-(4-oxopiperidin-1-yl)pyrimidine in 3 ml of tetrahydrofuran, followed by stirring under ice-cooling for 1 hour and then at room temperature for an addition 1 hour period. The reaction mixture was again cooled with ice, and a saturated ammonium chloride aqueous solution was added thereto dropwise. After stirring at room temperature for 10 minutes, the mixture was extracted with ethyl acetate. The extract was washed successively with a saturated ammonium chloride aqueous solution, a saturated sodium hydrogencarbonate aqueous solution and a saturated sodium chloride aqueous solution, and dried over anhydrous sodium sulfate. The desiccant was removed by filtration, the filtrate was concentrated under reduced pressure, and the residue was purified by silica gel column chromatography (developing solvent: hexane/ethyl acetate=4/1) to give 238 mg of 2-[N-(2-bromo-4-isopropylphenyl)-N-ethylamino]-4-[4-(3-chlorophenyl)-4-hydroxypiperidin-1-yl]-6-methylpyrimidine.

Workup

  1. temperatureunder reflux for 1 hour
  2. temperatureThe reaction mixture was cooled with ice
  3. temperaturecooling for 1 hour
  4. additionat room temperature for an addition 1 hour period
  5. temperatureThe reaction mixture was again cooled with ice
  6. stirringAfter stirring at room temperature for 10 minutes
  7. extractionthe mixture was extracted with ethyl acetate
  8. washThe extract was washed successively with a saturated ammonium chloride aqueous solution
  9. dry with materiala saturated sodium hydrogencarbonate aqueous solution and a saturated sodium chloride aqueous solution, and dried over anhydrous sodium sulfate
  10. customThe desiccant was removed by filtration
  11. concentrationthe filtrate was concentrated under reduced pressure
  12. customthe residue was purified by silica gel column chromatography (developing solvent: hexane/ethyl acetate=4/1)

Sources & evidence

ORD record
ord-682917ea631e422ca28ecde285c6eb40
Source dataset
uspto-grants-2001_02
Patent number
US06187781B1

Reaction notes

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