Phenol → 1-Benzhydryl-3-phenoxyazetidine

HRID 570802Notes

Reaction equation

HRID 570802 reaction equation
[C:1]1([OH:7])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[H-].[Na+].CS(O[CH:15]1[CH2:18][N:17]([CH:19]([C:26]2[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=2)[C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=2)[CH2:16]1)(=O)=O>C1(C)C=CC=CC=1>[C:20]1([CH:19]([C:26]2[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=2)[N:17]2[CH2:18][CH:15]([O:7][C:1]3[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=3)[CH2:16]2)[CH:21]=[CH:22][CH:23]=[CH:24][CH:25]=1

Participants

5

Reactant 3

HCID 996PhenolHCID 24758Sodium hydrideHCID 27587161-(Diphenylmethyl)azetidin-3-yl methanesulfonate

Product 1

HCID 28175781-Benzhydryl-3-phenoxyazetidineYield 84%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent2×

Conditions

Temperature
60 °C

Procedure

Phenol (6.68 g, 75 mmol) was added to a suspension of sodium hydride (60% dispersion in mineral oil, 2.82 g, 75 mmol) in toluene (50 mL) and the mixture was heated at 60° C. for 2 hours. The temperature was then increased to 80° C. and a solution of 1-(diphenylmethyl)-3-azetidinyl methanesulfonate (15 g, 47 mol) in toluene (150 mL) was added dropwise. The reaction mixture was stirred for 2 hours at 80° C., cooled then washed with water and dilute sodium hydroxide solution. The organic solution was dried over magnesium sulfate, concentrated in vacuo and the residue was re-crystallised from water/isopropanol to afford the title compound as a solid in 84% yield, 12.4 g. LRMS APCI m/z 316 [M+H]+

Workup

  1. temperatureThe temperature was then increased to 80° C.
  2. temperaturecooled
  3. washthen washed with water and dilute sodium hydroxide solution
  4. dry with materialThe organic solution was dried over magnesium sulfate
  5. concentrationconcentrated in vacuo
  6. customthe residue was re-crystallised from water/isopropanol

Sources & evidence

ORD record
ord-116a9051d2f545b99e871a3b52c32f20
Source dataset
uspto-grants-2015_05
Patent number
US09023872B2

Reaction notes

Loading…