Diethyl Ether → (1-Benzhydryl-azetidin-3-yl)-(4-chloro-phenyl)-methanone

HRID 1182088Notes

Reaction equation

HRID 1182088 reaction equation
[CH:1]([N:14]1[CH2:17][CH:16]([C:18]#N)[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.[Cl:20][C:21]1[CH:26]=[CH:25][C:24]([Mg]Br)=[CH:23][CH:22]=1.C([O:31]CC)C>ClC1C=CC=CC=1>[CH:1]([N:14]1[CH2:17][CH:16]([C:18]([C:24]2[CH:25]=[CH:26][C:21]([Cl:20])=[CH:22][CH:23]=2)=[O:31])[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

5

Reactant 3

HCID 3283Diethyl EtherHCID 27792901-(Diphenylmethyl)azetidine-3-carbonitrileHCID 178478191HCID 178478191, compound

Product 1

HCID 69361102(1-Benzhydryl-azetidin-3-yl)-(4-chloro-phenyl)-methanone

Reagents, catalysts & solvents 1

HCID 7964ChlorobenzeneSolvent

Conditions

Temperature
60 °C

Procedure

A solution of 1-Benzhydryl-azetidine-3-carbonitrile (23.6 g, 95 mmol) in chlorobenzene (250 ml) under nitrogen is treated with a 1.0 M solution of 4-chlorophenylmagnesium bromide in diethylether (100 ml, 100 mmol) over one hour, ensuring the temperature does not exceed 30° C. The stirred reaction mixture is heated to 60° C. for 1 hour, then cooled back to ambient temperature and quenched with a saturated aqueous solution of ammonium chloride (250 ml). The organic phase is washed with brine, dried over magnesium sulphate, and evaporated to a yellow oil. The oil is dissolved in methanol (300 ml), treated with concentrated hydrochloric acid (25 ml), and stirred at ambient temperature for 18 hours. The solvent is evaporated and the residue partitioned between ethylacetate (250 ml) and saturated sodium bicarbonate solution (250 ml). The aqueous phase is extracted with more ethylacetate and the combined organic phases, treated with magnesium sulphate and charcoal, filtered and evaporated to afford (1-Benzhydryl-azetidin-3-yl)-(4-chloro-phenyl)-methanone. [MH]+ 361.99

Workup

  1. customdoes not exceed 30° C
  2. customThe stirred reaction mixture
  3. temperaturecooled back to ambient temperature
  4. customquenched with a saturated aqueous solution of ammonium chloride (250 ml)
  5. washThe organic phase is washed with brine
  6. dry with materialdried over magnesium sulphate
  7. customevaporated to a yellow oil
  8. dissolutionThe oil is dissolved in methanol (300 ml)
  9. additiontreated with concentrated hydrochloric acid (25 ml)
  10. customThe solvent is evaporated
  11. customthe residue partitioned between ethylacetate (250 ml) and saturated sodium bicarbonate solution (250 ml)
  12. extractionThe aqueous phase is extracted with more ethylacetate
  13. additionthe combined organic phases, treated with magnesium sulphate and charcoal
  14. filtrationfiltered
  15. customevaporated

Sources & evidence

ORD record
ord-6528cc07518245d8819598e9e429b810
Source dataset
uspto-grants-2007_10
Patent number
US07288537B2

Reaction notes

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