Sodium Hydroxide → 1-(1-Phenylethyl)-3-[4-(trifluoromethyl)phenoxy]azetidine

HRID 2164524Notes

Reaction equation

HRID 2164524 reaction equation
[CH3:1][CH:2]([N:9]1[CH2:12][CH:11]([OH:13])[CH2:10]1)[C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1.[OH-].[Na+].[H-].[Na+].[F:18][C:19]([F:28])([F:27])[C:20]1[CH:25]=[CH:24][C:23](F)=[CH:22][CH:21]=1>CN(C)C=O.C1C=CC=CC=1>[CH3:1][CH:2]([N:9]1[CH2:12][CH:11]([O:13][C:23]2[CH:24]=[CH:25][C:20]([C:19]([F:28])([F:27])[F:18])=[CH:21][CH:22]=2)[CH2:10]1)[C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1

Participants

7

Reactant 4

HCID 14798Sodium HydroxideHCID 24758Sodium hydrideHCID 67873Benzene, 1-fluoro-4-(trifluoromethyl)-HCID 37924881-(1-phenylethyl)azetidin-3-ol

Product 1

HCID 128124861-(1-Phenylethyl)-3-[4-(trifluoromethyl)phenoxy]azetidineYield 39.8%

Reagents, catalysts & solvents 2

HCID 241BenzeneSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
90 °C

Procedure

The maleate salt of 1-(α-methylbenzyl)-3-hydroxyazetidine (78.6 g., 0.20 mole) was partitioned between benzene and dilute sodium hydroxide, the benzene layer dried, filtered, and concentrated at reduced pressure. The residue was dissolved in 100 ml. of dry dimethylformamide and added at a rapid dropwise rate, to a stirring suspension of 10.1 g. (0.22 mole) of sodium hydride (50% in mineral oil) in 150 ml. of dry dimethylformamide at 90° C. The solution was heated at 90° C. for one hour and then treated dropwise with 32.0 g. (0.20 mole) of 4-trifluoromethylfluorobenzene. The solution was refluxed for three hours. The cooled solution was partitioned between water and isopropyl ether, and the ether layer extracted with dilute hydrochloric acid. The aqueous acid layer was made basic with concentrated sodium hydroxide and ice, and extracted with isopropyl ether. The ether layer was concentrated and the residue distilled at 150°-160° C./0.2 mm. to give 25.6 g of product.

Workup

  1. dry with materialthe benzene layer dried
  2. filtrationfiltered
  3. concentrationconcentrated at reduced pressure
  4. dissolutionThe residue was dissolved in 100 ml
  5. additionof dry dimethylformamide and added at a rapid dropwise rate, to a stirring suspension of 10.1 g
  6. customat 90° C
  7. additiontreated dropwise with 32.0 g
  8. temperatureThe solution was refluxed for three hours
  9. customThe cooled solution was partitioned between water and isopropyl ether
  10. extractionthe ether layer extracted with dilute hydrochloric acid
  11. extractionextracted with isopropyl ether
  12. concentrationThe ether layer was concentrated
  13. distillationthe residue distilled at 150°-160° C./0.2 mm

Sources & evidence

ORD record
ord-2b7a91a4642544878e7350a8944e1b21
Source dataset
uspto-grants-1985_03
Patent number
US04505907

Reaction notes

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