Water → HCID 19799607, compound

HRID 2081376Notes

Reaction equation

HRID 2081376 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:28].Cl.C(N(CC)CC)C.[OH-:39].[Na+].[CH3:41][O:42][C:43]1[CH:44]=[C:45](O)[CH:46]=[CH:47][CH:48]=1.[OH2:50]>C1(C)C=CC=CC=1.[Br-].C([N+](CCCC)(CCCC)CCCC)CCC>[C:10]([OH:12])(=[O:28])[C:11]([OH:50])=[O:39].[C:13]1([CH:7]([C:1]2[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=2)[N:8]2[CH2:11][CH:10]([O:12][C:47]3[CH:46]=[CH:45][CH:44]=[C:43]([O:42][CH3:41])[CH:48]=3)[CH2:9]2)[CH:14]=[CH:15][CH:16]=[CH:17][CH:18]=1

Participants

10

Reactant 7

HCID 962Water2×HCID 8471TriethylamineHCID 90073-MethoxyphenolHCID 11130Triethylamine hydrochlorideHCID 14798Sodium HydroxideHCID 31297Methanesulfonyl chlorideHCID 3304481-(Diphenylmethyl)azetidin-3-ol

Product 1

HCID 19799607HCID 19799607, compoundYield 71.8%

Reagents, catalysts & solvents 2

HCID 74236Tetrabutylammonium BromideCatalystHCID 1140TolueneSolvent

Procedure

A stirred 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 cooled in a water bath while 27.5 g (0.22 mole) of methanesulfonyl chloride was added dropwise. After stirring for 18 hr, the reaction mixture was treated with 200 ml of water to dissolve the triethylamine hydrochloride. The toluene portion was separated and washed with 2×200 ml of water and added to a solution of 24 g (0.6 mole) of sodium hydroxide in 100 ml of water. This mixture was stirred vigorously while 25 g (0.2 mole) of 3-methoxyphenol was added along with 100 ml of tetrabutylammonium bromide and then heated at reflux for 72 hr. After an additional 48 hr of stirring without heat, the basic portion was separated and the toluene portion washed with 3×100 ml of water, dried over magnesium sulfate, then concentrated in vacuo (64 g). Thin layer chromatography (20% ethyl acetate-toluene on silica gel) showed approximately 30% starting azetidinol present. The crude material was placed on a 1200 g silica gel column and eluted with toluene until the material at the solvent front came off the column. The elution solvent was changed to an ethyl acetate-toluene gradient ranging from 2-40% ethyl acetate. Most of the material came off between 5-20% ethyl acetate. A total of nine fractions were shown to be usable by TLC and combined and concentrated in vacuo, to give 49.64 g of oil (71.8%). A portion of this oil was converted to the oxalate salt in acetone isopropyl ether and recrystallized from methylisobutyl ketone, yielding fine white crystals, m.p. 133°-134° C.

Workup

  1. additionwas added dropwise
  2. customThe toluene portion was separated
  3. washwashed with 2×200 ml of water
  4. temperatureheated
  5. temperatureat reflux for 72 hr
  6. stirringAfter an additional 48 hr of stirring
  7. temperaturewithout heat
  8. customthe basic portion was separated
  9. washthe toluene portion washed with 3×100 ml of water
  10. dry with materialdried over magnesium sulfate
  11. concentrationconcentrated in vacuo (64 g)
  12. washeluted with toluene until the material at the solvent front
  13. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-989b695477e34527be40181342ed57ba
Source dataset
uspto-grants-1993_02
Patent number
US05183902

Reaction notes

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