Potassium Carbonate → 3-(2-Chloro-4-fluorophenoxy)-1-(diphenylmethyl)azetidine

HRID 222344

Reaction equation

HRID 222344 reaction equation
CS([O:5][CH:6]1[CH2:9][N:8]([CH:10]([C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)[C:11]2[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=2)[CH2:7]1)(=O)=O.C(=O)([O-])[O-].[K+].[K+].[Cl:29][C:30]1[CH:35]=[C:34]([F:36])[CH:33]=[CH:32][C:31]=1O>C(#N)C>[Cl:29][C:30]1[CH:35]=[C:34]([F:36])[CH:33]=[CH:32][C:31]=1[O:5][CH:6]1[CH2:9][N:8]([CH:10]([C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)[C:11]2[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=2)[CH2:7]1

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 748142-Chloro-4-fluorophenolHCID 27587161-(Diphenylmethyl)azetidin-3-yl methanesulfonate

Product 1

HCID 150422263-(2-Chloro-4-fluorophenoxy)-1-(diphenylmethyl)azetidine

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

A mixture of 1-(diphenylmethyl)-3-azetidinyl methanesulfonate (363.8 g, 1.15 mol), potassium carbonate (330 g, 2.38 mol) and 2-chloro-4-fluorophenol (140 g, 0.96 mol) in acetonitrile (2.5 L) was heated under reflux for 4.5 hours. The cooled reaction mixture was then concentrated in vacuo and the residue was partitioned between ethyl acetate (1 L) and water (500 mL). The organic layer was separated, dried over sodium sulfate concentrated in vacuo and the residue was triturated with ethyl acetate/pentane/dichloromethane, 90:10:1, to afford the title compound as a white solid in quantitative yield, 350 g. 1H NMR (400 MHz, CDCl3) δ: 3.19 (m, 2H), 3.75 (m, 2H), 4.45 (m, 1H), 4.78 (m, 1H), 6.60 (m, 1H), 6.83 (m, 1H), 7.14 (m, 1H), 7.18-7.50 (m, 10H)

Workup

  1. temperaturewas heated
  2. temperatureunder reflux for 4.5 hours
  3. customThe cooled reaction mixture
  4. concentrationwas then concentrated in vacuo
  5. customthe residue was partitioned between ethyl acetate (1 L) and water (500 mL)
  6. customThe organic layer was separated
  7. dry with materialdried over sodium sulfate
  8. concentrationconcentrated in vacuo
  9. customthe residue was triturated with ethyl acetate/pentane/dichloromethane, 90:10:1

Sources & evidence

ORD record
ord-8a5b59d24eba460ba66f0775088bfbec
Source dataset
uspto-grants-2012_06
Patent number
US08207198B2

Linked notes

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