3-(Trifluoromethyl)phenol → 1-Benzhydryl-3-[3-(trifluoromethyl)phenoxy]azetidine

HRID 1711757Notes

Reaction equation

HRID 1711757 reaction equation
[CH:1]([N:14]1[CH2:17][CH:16]([O:18]S(C)(=O)=O)[CH2:15]1)([C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.O[C:24]1[CH:25]=[C:26]([C:30]([F:33])([F:32])[F:31])[CH:27]=[CH:28][CH:29]=1.[OH-].[Na+]>[Br-].C([N+](CCCC)(CCCC)CCCC)CCC.C1(C)C=CC=CC=1.O>[CH:1]([N:14]1[CH2:17][CH:16]([O:18][C:24]2[CH:29]=[CH:28][CH:27]=[C:26]([C:30]([F:33])([F:32])[F:31])[CH:25]=2)[CH2:15]1)([C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

7

Reactant 3

HCID 73763-(Trifluoromethyl)phenolHCID 14798Sodium HydroxideHCID 27587161-(Diphenylmethyl)azetidin-3-yl methanesulfonate

Product 1

HCID 117286941-Benzhydryl-3-[3-(trifluoromethyl)phenoxy]azetidine

Reagents, catalysts & solvents 3

HCID 74236Tetrabutylammonium BromideCatalystHCID 962WaterSolvent2×HCID 1140TolueneSolvent

Procedure

A suspension of 1 mmol methanesulfonic acid 1-benzhydryl-azetidin-3-yl ester [33301-41-6], 1 mmol 3-hydroxy benzotrifluoride, 0.05 mmol tetrabutyl ammonium bromide and 4 mmol sodium hydroxide in a mixture of 5 ml toluene and 0.2 ml water was refluxed overnight. The reaction mixture was cooled, diluted with 20 ml of water and extracted 3 times with dichloromethane. The organic phase was dried, concentrated and the crude product purified by chromatography (methanol/dichloromethane). MS (m/e): 442.3 ([M+CH3COO−]−, 100%).

Workup

  1. temperaturewas refluxed overnight
  2. temperatureThe reaction mixture was cooled
  3. extractionextracted 3 times with dichloromethane
  4. customThe organic phase was dried
  5. concentrationconcentrated
  6. customthe crude product purified by chromatography (methanol/dichloromethane)

Sources & evidence

ORD record
ord-81322e2063254b3195fe440834edc3f3
Source dataset
uspto-grants-2010_09
Patent number
US07790763B2

Reaction notes

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