1-(Diphenylmethyl)azetidin-3-one → 1-Benzhydryl-3-(4-chloro-phenyl)-azetidin-3-ol

HRID 2307217Notes

Reaction equation

HRID 2307217 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([Mg]Br)=[CH:4][CH:3]=1.[C:10]1([CH:16]([C:22]2[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=2)[N:17]2[CH2:20][C:19](=[O:21])[CH2:18]2)[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1>C(OCC)C>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:19]2([OH:21])[CH2:20][N:17]([CH:16]([C:22]3[CH:23]=[CH:24][CH:25]=[CH:26][CH:27]=3)[C:10]3[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=3)[CH2:18]2)=[CH:4][CH:3]=1

Participants

4

Reactant 2

HCID 37355581-(Diphenylmethyl)azetidin-3-oneHCID 178478191HCID 178478191, compound

Product 1

HCID 541715491-Benzhydryl-3-(4-chloro-phenyl)-azetidin-3-ol

Reagents, catalysts & solvents 1

HCID 3283Diethyl EtherSolvent2×

Conditions

Temperature
-78 °C

Procedure

To a stirred solution of 4-chlorophenylmagnesium bromide (9.1 mL, 10 M in diethyl ether) in diethyl ether (80 mL) at −78° C. under an argon atmosphere was added compound 3 (1.8 g, 7.6 mmol) in diethyl ether (50 mL) dropwise over 20 minutes. The reaction mixture was stirred at −78° C. for 2 hours, then slowly warmed to room temperature with stirring over 18 hours. The reaction mixture was then partitioned between aqueous ammonium acetate solution (50 mL) and diethyl ether (50 mL). The aqueous layer was extracted with diethyl ether (3×50 mL) and the combined organic extracts were washed (water, brine), dried (Na2SO4), filtered and concentrated in vacuo to give the crude product as a pale yellow viscous oil in quantitative yield. A sample purified for analysis by column chromatography on silica gel using 15-30% ethyl acetate-hexane as eluent and subsequent crystallisation from bexane gave 3-(4-chorophenyl)-1-(diphenyhnethyl)-3-azetidinol (4), m.p. 108° C. Found: C, 75.42; H, 5.79; N, 3.98. C22H20CINO requires C, 75.53; H, 5.76; N, 4.00%.

Workup

  1. temperatureslowly warmed to room temperature
  2. stirringwith stirring over 18 hours
  3. customThe reaction mixture was then partitioned between aqueous ammonium acetate solution (50 mL) and diethyl ether (50 mL)
  4. extractionThe aqueous layer was extracted with diethyl ether (3×50 mL)
  5. washthe combined organic extracts were washed (water, brine)
  6. dry with materialdried (Na2SO4)
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. customto give the crude product as a pale yellow viscous oil in quantitative yield
  10. customA sample purified for analysis by column chromatography on silica gel using 15-30% ethyl acetate-hexane as eluent
  11. customsubsequent crystallisation from bexane

Sources & evidence

ORD record
ord-911df43bdd674530a168f55b37e98ade
Source dataset
uspto-grants-2004_12
Patent number
US06831078B1

Reaction notes

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