Toluene → 1-[4-(Phenylmethoxy)phenyl]-4-[4-(trifluoromethoxy)phenoxy]piperidine

HRID 1039609Notes

Reaction equation

HRID 1039609 reaction equation
[F:1][C:2]([F:18])([F:17])[O:3][C:4]1[CH:16]=[CH:15][C:7]([O:8][CH:9]2[CH2:14][CH2:13][NH:12][CH2:11][CH2:10]2)=[CH:6][CH:5]=1.Br[C:20]1[CH:25]=[CH:24][C:23]([O:26][CH2:27][C:28]2[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=2)=[CH:22][CH:21]=1.CC(C)([O-])C.[Na+].C1(C)C=CC=CC=1>C(OCC)(=O)C.C([O-])(=O)C.[Pd+2].C([O-])(=O)C.C1([B-](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C([PH+](C(C)(C)C)C(C)(C)C)(C)(C)C.O>[CH2:27]([O:26][C:23]1[CH:24]=[CH:25][C:20]([N:12]2[CH2:11][CH2:10][CH:9]([O:8][C:7]3[CH:15]=[CH:16][C:4]([O:3][C:2]([F:1])([F:17])[F:18])=[CH:5][CH:6]=3)[CH2:14][CH2:13]2)=[CH:21][CH:22]=1)[C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1

Participants

9

Reactant 4

HCID 1140TolueneHCID 1388351-Bromo-4-phenylmethoxybenzeneHCID 161154394-[4-(Trifluoromethoxy)phenoxy]piperidineHCID 23676156Sodium t-butoxide

Product 1

HCID 684830771-[4-(Phenylmethoxy)phenyl]-4-[4-(trifluoromethoxy)phenoxy]piperidineYield 98.4%

Reagents, catalysts & solvents 4

HCID 167845palladium(II) acetateCatalystHCID 23136663Tri-tert-butylphosphonium TetraphenylborateCatalystHCID 962WaterSolventHCID 8857Ethyl AcetateSolvent2×

Procedure

4-[4-(Trifluoromethoxy)phenoxy]piperidine (2.61 g), benzyl 4-bromophenyl ether (2.63 g), palladium (II) acetate (0.67 mg), Tri-tert-butyl phosphonium tetraphenyl borate (1.57 mg), sodium tert-butoxide (1.06 g) and toluene (13 mL) were placed in a vessel and heated to reflux for 6 hr under Ar. The reaction mixture was then cooled to room temperature and water (100 mL) and ethyl acetate (100 mL) were added. The organic material was taken up in ethyl acetate. The organic layer was washed three times with water (100 mL×3). The organic layer was filtered to remove harz and then the organic layer was condensed under reduced pressure to afford 4.36 g (98.4% yield) of a pale yellow crystal target compound.

Workup

  1. temperatureheated
  2. temperatureto reflux for 6 hr under Ar
  3. washThe organic layer was washed three times with water (100 mL×3)
  4. filtrationThe organic layer was filtered
  5. customto remove harz
  6. customcondensed under reduced pressure

Sources & evidence

ORD record
ord-eda3b3c11fd94f64a01bdd352d557dd0
Source dataset
uspto-grants-2013_10
Patent number
US08552188B2

Reaction notes

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