1-Chloro-4-(chloromethyl)benzene → 3-(4-Chlorobenzyloxy)-1-(diphenylmethyl) azetidine

HRID 2185629Notes

Reaction equation

HRID 2185629 reaction equation
[C:1]1([CH:7]([C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)[N:8]2[CH2:11][CH:10]([OH:12])[CH2:9]2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[H-].[Na+].[Cl:21][C:22]1[CH:29]=[CH:28][C:25]([CH2:26]Cl)=[CH:24][CH:23]=1>CN(C=O)C>[Cl:21][C:22]1[CH:29]=[CH:28][C:25]([CH2:26][O:12][CH:10]2[CH2:11][N:8]([CH:7]([C:1]3[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=3)[C:13]3[CH:14]=[CH:15][CH:16]=[CH:17][CH:18]=3)[CH2:9]2)=[CH:24][CH:23]=1

Participants

5

Reactant 3

HCID 77231-Chloro-4-(chloromethyl)benzeneHCID 24758Sodium hydrideHCID 3304481-(Diphenylmethyl)azetidin-3-ol

Product 1

HCID 543278103-(4-Chlorobenzyloxy)-1-(diphenylmethyl) azetidineYield 80.2%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

A solution of 1-diphenylmethyl-3-azetidinol (25 mmol) in DMF (100 mL) was added at 0° C. to a suspension of NaH (60% disp.in oil, 30 mmol) in DMF (50 mL). The reaction mixture was stirred at room temperature for 1 h, then 4-chlorobenzylchloride (25 mmol) was added dropwise at 0° C. and the reaction mixture stirred at room temperature for 3 h. The reaction was quenched with water and extracted with ethyl acetate (3×50 mL), the extracts were washed with water and brine, dried (MgSO4) and concentrated in vacuo. The residue was purified by chromatography [SiO2; hexane-ethyl acetate (9:1)] to yield the product as a yellow oil (7.3 g, 80%). The material was used in the next step without further purification.

Workup

  1. stirringthe reaction mixture stirred at room temperature for 3 h
  2. customThe reaction was quenched with water
  3. extractionextracted with ethyl acetate (3×50 mL)
  4. washthe extracts were washed with water and brine
  5. dry with materialdried (MgSO4)
  6. concentrationconcentrated in vacuo
  7. customThe residue was purified by chromatography [SiO2; hexane-ethyl acetate (9:1)]

Sources & evidence

ORD record
ord-78c7753959d845e8ab7a39a618032fda
Source dataset
uspto-grants-2002_06
Patent number
US06403574B1

Reaction notes

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