p-Chlorothiophenol → 1-benzhydryl-3-(4-chloro-phenylthio)-azetidine

HRID 2081385Notes

Reaction equation

HRID 2081385 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](O)[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.[OH-].[Na+].[Cl:40][C:41]1[CH:46]=[CH:45][C:44]([SH:47])=[CH:43][CH:42]=1>C1(C)C=CC=CC=1.O.[Br-].C([N+](CCCC)(CCCC)CCCC)CCC>[Cl:40][C:41]1[CH:46]=[CH:45][C:44]([S:47][CH:10]2[CH2:11][N:8]([CH:7]([C:13]3[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=3)[C:1]3[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=3)[CH2:9]2)=[CH:43][CH:42]=1

Participants

10

Reactant 6

HCID 7815p-ChlorothiophenolHCID 7914Diisopropyl EtherHCID 8471TriethylamineHCID 14798Sodium HydroxideHCID 31297Methanesulfonyl chlorideHCID 3304481-(Diphenylmethyl)azetidin-3-ol

Product 1

HCID 28226111-benzhydryl-3-(4-chloro-phenylthio)-azetidine

Reagents, catalysts & solvents 3

HCID 74236Tetrabutylammonium BromideCatalystHCID 962WaterSolventHCID 1140TolueneSolvent

Procedure

A stirred mixture of 48 g (0.2 mole) of 1-diphenylmethyl-3-azetidinol, and 22 g (28 ml) (0.22 mole) of triethylamine in 800 ml of toluene under nitrogen was cooled in a water bath then treated with 27.5 g (0.22 mole) of methanesulfonyl chloride added dropwise. After stirring for 16 hr, the reaction mixture was diluted by adding 200 ml of isopropyl ether. The triethylamine hydrochloride was removed by filtration and washed with 200 ml of (50/50) toluene/isopropyl ether. The filtrates were combined, washed with 2×200 ml of water and returned to the reaction mixture. The reaction mixture was treated with 24 g (0.6 mole) of sodium hydroxide in 100 ml of water, 6.5 g (0.02 mole) of tetrabutylammonium bromide and 31.8 g (0.22 mole) of 4-chlorothiophenol then heated at reflux while stirring vigorously. After 96 hr, TLC showed the expected product to be approximately 80% of the reaction mixture. After cooling, the organic phase was separated, washed with water (3×200 ml) and treated with 25 g of oxalic acid dihydrate in 100 ml of methanol. The precipitated product was collected by filtration, yielding 75 g of crude oxalate salt. The oxalate salt was suspended in warm water and treated with 0.4 mole (26 g) of potassium hydroxide. The solid which precipitated from the basic solution was collected and recrystallized from methanol with charcoal treatment to yield 17.6 g of white granular crystals, m.p. 84°-86° C. A second crop of crystals was obtained from the filtrate after standing (8.6 g). The yield was 36%.

Workup

  1. temperaturewas cooled in a water bath
  2. additionadded dropwise
  3. additionthe reaction mixture was diluted
  4. customThe triethylamine hydrochloride was removed by filtration
  5. washwashed with 200 ml of (50/50) toluene/isopropyl ether
  6. washwashed with 2×200 ml of water
  7. temperaturethen heated
  8. temperatureat reflux
  9. stirringwhile stirring vigorously
  10. waitAfter 96 hr

Sources & evidence

ORD record
ord-c470b0aa67ae462bb4e124a73223d8a3
Source dataset
uspto-grants-1993_02
Patent number
US05183902

Reaction notes

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