Benzene, 1-bromo-3-(trifluoromethyl)- → HCID 69201465, compound

HRID 2376639Notes

Reaction equation

HRID 2376639 reaction equation
[Mg].Br[C:3]1[CH:8]=[CH:7][CH:6]=[C:5]([C:9]([F:12])([F:11])[F:10])[CH:4]=1.[CH2:13]([N:20]1[CH2:25][CH2:24][C:23](=[O:26])[CH2:22][CH2:21]1)[C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1.[Cl-:27].[NH4+]>C1COCC1.O.CCOCC>[ClH:27].[CH2:13]([N:20]1[CH2:25][CH2:24][C:23]([C:3]2[CH:8]=[CH:7][CH:6]=[C:5]([C:9]([F:12])([F:11])[F:10])[CH:4]=2)([OH:26])[CH2:22][CH2:21]1)[C:14]1[CH:15]=[CH:16][CH:17]=[CH:18][CH:19]=1

Participants

8

Reactant 4

HCID 9817Benzene, 1-bromo-3-(trifluoromethyl)-HCID 192201-Benzyl-4-piperidoneHCID 25517Ammonium ChlorideHCID 5462224Magnesium

Product 1

HCID 69201465HCID 69201465, compoundYield 55%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 3283Diethyl EtherSolventHCID 8028TetrahydrofuranSolvent4×

Conditions

Temperature
30 °C

Procedure

A mixture of 180 g of magnesium in 2670 ml of THF is heated to 30° C. and admixed with 33 ml of a solution of 1670 g of 1-bromo-3-(trifluoromethyl)benzene in 1330 ml of THF and then, slowly, with the remainder of the solution so as to bring about and subsequently maintain reflux of the THF, and is left at reflux with stirring for 2 hours. Subsequently a solution of 1000 g of 1-benzyl-4-piperidinone in 3200 ml of THF is added slowly and the mixture is heated at reflux for 2 hours. After cooling to AT, the reaction mixture is introduced over 30 minutes into a solution of 1870 g of ammonium chloride in 6700 ml of water and the mixture is left with stirring at 20-25° C. for 2 hours. After decanting, the organic phase is washed with 5330 ml of water and the solvent is evaporated under vacuum. The residue is taken up in 5330 ml of ether, a solution of 210 g of HCl gas in 800 ml of propan-2-ol is added slowly, the temperature being kept below 25° C., the mixture is left with stirring for 40 minutes and the crystals formed are isolated with suction. The crystals are taken up in 2000 ml of ether and again isolated with suction. 1080 g of the expected product are obtained following recrystallization from a propan-2-ol/EtOH (70/30; v/v) mixture.

Workup

  1. temperaturesubsequently maintain
  2. waitis left
  3. temperatureat reflux
  4. temperaturethe mixture is heated
  5. temperatureat reflux for 2 hours
  6. temperatureAfter cooling to AT
  7. waitthe mixture is left
  8. stirringwith stirring at 20-25° C. for 2 hours
  9. customAfter decanting
  10. washthe organic phase is washed with 5330 ml of water
  11. customthe solvent is evaporated under vacuum
  12. additiona solution of 210 g of HCl gas in 800 ml of propan-2-ol is added slowly
  13. custombeing kept below 25° C.
  14. waitthe mixture is left
  15. stirringwith stirring for 40 minutes
  16. customthe crystals formed
  17. customare isolated with suction
  18. customagain isolated with suction

Sources & evidence

ORD record
ord-9a15bf23490e4d92912c36e4e1b3c469
Source dataset
uspto-grants-2008_12
Patent number
US07468368B2

Reaction notes

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