Iodine → 1-Benzyl-4-[2-fluoro-5-(trifluoromethyl)benzyl]piperidin-4-ol

HRID 270040Notes

Reaction equation

HRID 270040 reaction equation
II.Br[CH2:4][C:5]1[CH:10]=[C:9]([C:11]([F:14])([F:13])[F:12])[CH:8]=[CH:7][C:6]=1[F:15].[CH2:16]([N:23]1[CH2:28][CH2:27][C:26](=[O:29])[CH2:25][CH2:24]1)[C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1.[NH4+].[Cl-]>CCOCC>[CH2:16]([N:23]1[CH2:28][CH2:27][C:26]([CH2:4][C:5]2[CH:10]=[C:9]([C:11]([F:14])([F:13])[F:12])[CH:8]=[CH:7][C:6]=2[F:15])([OH:29])[CH2:25][CH2:24]1)[C:17]1[CH:18]=[CH:19][CH:20]=[CH:21][CH:22]=1

Participants

6

Reactant 4

HCID 807IodineHCID 192201-Benzyl-4-piperidoneHCID 25517Ammonium ChlorideHCID 27375712-(Bromomethyl)-1-fluoro-4-(trifluoromethyl)benzene2×

Product 1

HCID 689624821-Benzyl-4-[2-fluoro-5-(trifluoromethyl)benzyl]piperidin-4-ol

Reagents, catalysts & solvents 1

HCID 3283Diethyl EtherSolvent3×

Procedure

To a stirring suspension of Mg strips (308 mg) in Et2O (5 mL) was added a crystal of iodine followed by 0.3 mL of 2-(bromomethyl)-1-fluoro-4-(trifluoromethyl)benzene under argon. The reaction was initiated with a high intensity heat gun, then 2-(bromomethyl)-1-fluoro-4-(trifluoromethyl)benzene (2.5 g, 9.73 mmol) in Et2O (5 mL) was added slowly (maintaining reflux). After addition was completed the reaction mixture was refluxed for 50 min, cooled to room temperature. A solution of 1-benzylpiperidin-4-one (1.84 g, 9.73 mmol) in Et2O (10 mL) was added slowly with vigorous stirring. After addition was completed, the reaction mixture was left at room temperature for 50 min, saturated aqueous NH4Cl solution was added and stirred at room temperature untill hydrolysis was finished, extracted with ethyl acetate. The combined organic layer was washed with water, dtied over Na2SO4, filtered and concentrated. The residue was purified by silica gel flash chromatography (0-1% methanol in dichloromethane, 0.2% NH4OH) to give the subtitled compound (720 mg).

Workup

  1. temperatureheat gun
  2. temperature(maintaining reflux)
  3. additionAfter addition
  4. temperaturewas refluxed for 50 min
  5. additionAfter addition
  6. customuntill hydrolysis
  7. extractionextracted with ethyl acetate
  8. washThe combined organic layer was washed with water
  9. filtrationfiltered
  10. concentrationconcentrated
  11. customThe residue was purified by silica gel flash chromatography (0-1% methanol in dichloromethane, 0.2% NH4OH)

Sources & evidence

ORD record
ord-cc5e2a82d42b4024ada4b9feecfc3c3b
Source dataset
uspto-grants-2008_11
Patent number
US07449475B2

Reaction notes

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