Benzene, 1-chloro-4-fluoro- → 1-Benzhydryl-3-(4-chlorophenoxy)azetane

HRID 1032086Notes

Reaction equation

HRID 1032086 reaction equation
[H-].[Na+].[C:3]1([CH:9]([C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=2)[N:10]2[CH2:13][CH:12]([OH:14])[CH2:11]2)[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1.[H][H].[Cl:23][C:24]1[CH:29]=[CH:28][C:27](F)=[CH:26][CH:25]=1>CN(C)C=O>[Cl:23][C:24]1[CH:29]=[CH:28][C:27]([O:14][CH:12]2[CH2:13][N:10]([CH:9]([C:3]3[CH:4]=[CH:5][CH:6]=[CH:7][CH:8]=3)[C:15]3[CH:16]=[CH:17][CH:18]=[CH:19][CH:20]=3)[CH2:11]2)=[CH:26][CH:25]=1

Participants

6

Reactant 4

HCID 9604Benzene, 1-chloro-4-fluoro-HCID 24758Sodium hydrideHCID 3304481-(Diphenylmethyl)azetidin-3-olHCID 178418361HCID 178418361, compound

Product 1

HCID 5974941-Benzhydryl-3-(4-chlorophenoxy)azetaneYield 82.4%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Conditions

Temperature
90 °C

Procedure

A stirred slurry of 41.3 g (1.03 mole) of 60% sodium hydride (in mineral oil) in 500 ml of dry dimethylformamide under nitrogen atmosphere was heated to 50° C. and 22.5 g (0.94 mole) of 1-diphenylmethyl-3-azetidinol in 700 ml of dry dimethylformamide was added dropwise at a rate which maintained the temperature between 70°-80° C. and allowed a gentle evolution of hydrogen. After the addition was complete, the reaction mixture was stirred for 2 hr at 90° C., then 125 g (0.94 mole) of 1-chloro-4-fluorobenzene was added dropwise. The reaction mixture was stirred at 90° C. under nitrogen for 24 hr, then stirred an additional 24 hr while the reaction mixture cooled to ambient temperature. The reaction mixture was poured into 6 liter of ice water and the solid which formed was collected by filtration to yield 271 g of wet crude product. A sample was recrystallized for elemental analysis from ethanol, yielding a fine tan crystalline product in 82.4% yield, m.p. 113°-114° C.

Workup

  1. temperaturemaintained the temperature between 70°-80° C.
  2. additionAfter the addition
  3. stirringThe reaction mixture was stirred at 90° C. under nitrogen for 24 hr
  4. stirringstirred an additional 24 hr while the reaction mixture
  5. temperaturecooled to ambient temperature
  6. customthe solid which formed
  7. filtrationwas collected by filtration

Sources & evidence

ORD record
ord-1e9a4ba6fb2f4e6abbd4d280180635aa
Source dataset
uspto-grants-1990_09
Patent number
US04956359

Reaction notes

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