Ammonium Chloride → HCID 70873701, compound

HRID 2172229Notes

Reaction equation

HRID 2172229 reaction equation
[CH2:1]([O:8][C:9]1[CH:14]=[CH:13][C:12](Br)=[C:11]([F:16])[CH:10]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[F:17][C:18]([F:34])([F:33])[O:19][C:20]1[CH:32]=[CH:31][C:23]([O:24][CH:25]2[CH2:30][CH2:29][NH:28][CH2:27][CH2:26]2)=[CH:22][CH:21]=1.CC(C)([O-])C.[Na+].C1(P(C2C=CC=CC=2)C2C=CC3C(=CC=CC=3)C=2C2C3C(=CC=CC=3)C=CC=2P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[Cl-].[NH4+]>C([O-])(=O)C.[Pd+2].C([O-])(=O)C.C1(C)C=CC=CC=1>[CH2:1]([O:8][C:9]1[CH:14]=[CH:13][C:12]([N:28]2[CH2:29][CH2:30][CH:25]([O:24][C:23]3[CH:22]=[CH:21][C:20]([O:19][C:18]([F:17])([F:33])[F:34])=[CH:32][CH:31]=3)[CH2:26][CH2:27]2)=[C:11]([F:16])[CH:10]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

8

Reactant 5

HCID 25517Ammonium ChlorideHCID 634876Binap, (A+-)-HCID 161154394-[4-(Trifluoromethoxy)phenoxy]piperidineHCID 222739334-(Benzyloxy)-1-bromo-2-fluorobenzeneHCID 23676156Sodium t-butoxide

Product 1

HCID 70873701HCID 70873701, compoundYield 71%

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 1140TolueneSolvent

Procedure

4-Benzyloxy-1-bromo-2-fluorobenzene (3.55 g, 12.6 mmol), 4-(4-trifluoromethoxyphenoxy)piperidine (3.0 g, 11.5 mmol), sodium tert-butoxide (1.55 g, 16.1 mmol) and toluene (60 ml) were mixed. Palladium acetate (0.10 g, 0.46 mmol) and 2,2′-bis(diphenylphosphino)-1,1′-binaphthyl (0.57 g, 0.92 mmol) were added thereto. The mixture was heated and refluxed under a nitrogen atmosphere for 4 hours. A saturated ammonium chloride aqueous solution was added to the reaction mixture, followed by extraction with ethyl acetate. The organic layer was washed with a saturated sodium chloride aqueous solution and dried over sodium sulfate. After filtering, the filtrate was concentrated under reduced pressure. The residue thus obtained was purified by silica gel column chromatography (hexane:ethyl acetate=80:20→60:40), and the resulting crude crystal was washed with hexane-diethylether to afford the title compound as a white powder (3.76 g, yield 71%).

Workup

  1. temperatureThe mixture was heated
  2. temperaturerefluxed under a nitrogen atmosphere for 4 hours
  3. extractionfollowed by extraction with ethyl acetate
  4. washThe organic layer was washed with a saturated sodium chloride aqueous solution
  5. dry with materialdried over sodium sulfate
  6. filtrationAfter filtering
  7. concentrationthe filtrate was concentrated under reduced pressure
  8. customThe residue thus obtained
  9. customwas purified by silica gel column chromatography (hexane:ethyl acetate=80:20→60:40)
  10. washthe resulting crude crystal was washed with hexane-diethylether

Sources & evidence

ORD record
ord-e2c0e4982dc24215974e0ff358257917
Source dataset
uspto-grants-2015_06
Patent number
US09051333B2

Reaction notes

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