3,4-Dichlorophenol → 3-(3,4-Dichlorophenoxy)-1-(diphenylmethyl)azetidine

HRID 1032085Notes

Reaction equation

HRID 1032085 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.C(N(CC)CC)C.CS(Cl)(=O)=O.C(OC(C)C)(C)C.[Cl:38][C:39]1[CH:40]=[C:41](O)[CH:42]=[CH:43][C:44]=1[Cl:45].[OH-].[Na+].N1(O)CCC1>C1(C)C=CC=CC=1.[Br-].C([N+](CCCC)(CCCC)CCCC)CCC.O>[Cl:38][C:39]1[CH:40]=[C:41]([CH:42]=[CH:43][C:44]=1[Cl:45])[O:12][CH:10]1[CH2:11][N:8]([CH:7]([C:1]2[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=2)[C:13]2[CH:14]=[CH:15][CH:16]=[CH:17][CH:18]=2)[CH2:9]1

Participants

11

Reactant 7

HCID 72583,4-DichlorophenolHCID 7914Diisopropyl EtherHCID 8471TriethylamineHCID 14798Sodium HydroxideHCID 31297Methanesulfonyl chlorideHCID 3304481-(Diphenylmethyl)azetidin-3-olHCID 22315763HCID 22315763, compound

Product 1

HCID 150422273-(3,4-Dichlorophenoxy)-1-(diphenylmethyl)azetidineYield 59.7%

Reagents, catalysts & solvents 3

HCID 74236Tetrabutylammonium BromideCatalystHCID 962WaterSolventHCID 1140TolueneSolvent2×

Procedure

A mixture of 48 g (0.2 mole) of 1-diphenylmethyl-3-azetidinol and 22 g (0.22 mole) of triethylamine in 800 ml of toluene was stirred in a water bath while 27.5 g (0.22 mole) of methanesulfonyl chloride was added dropwise and stirring was continued for 18 hr. The reaction mixture was treated with 400 ml of isopropyl ether then filtered. The filter cake was washed with 2×150 ml of 50/50 isopropyl ether and toluene. The combined filtrates were treated with 32.6 g (0.2 mole) of 3,4-dichlorophenol, 100 mg of tetrabutylammonium bromide and 24 g (0.6 mole) of sodium hydroxide in 100 ml of water. This mixture was stirred vigorously at reflux for 16 hr. The basic aqueous portion was separated and the organic portion washed with water, dried over magnesium sulfate then concentrated to a solid residue, 74.5 g. Several recrystallizations from ethanol-water gave a product which was contaminated with starting azetidinol. Therefore, the material, 57.4 g, was dissolved in toluene and treated with silica gel. After stirring for 6 hr, the silica gel was removed by filtration and washed with 50/50 ethyl acetate and toluene. The filtratrs were concentrated to yield 45.9 g (59.7%) of pure product. A sample for elemental analysis was recrystallized from ethanol, m.p. 114°-115° C.

Workup

  1. additionwas added dropwise
  2. filtrationthen filtered
  3. washThe filter cake was washed with 2×150 ml of 50/50 isopropyl ether and toluene
  4. stirringThis mixture was stirred vigorously
  5. temperatureat reflux for 16 hr
  6. customThe basic aqueous portion was separated
  7. washthe organic portion washed with water
  8. dry with materialdried over magnesium sulfate
  9. concentrationthen concentrated to a solid residue, 74.5 g
  10. customSeveral recrystallizations from ethanol-water
  11. customgave a product which
  12. additiontreated with silica gel
  13. stirringAfter stirring for 6 hr
  14. customthe silica gel was removed by filtration
  15. washwashed with 50/50 ethyl acetate and toluene
  16. concentrationThe filtratrs were concentrated

Sources & evidence

ORD record
ord-67b492ca476c4a9699a0be4606aed66d
Source dataset
uspto-grants-1990_09
Patent number
US04956359

Reaction notes

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