Hydrochloric Acid → (-)-1-[(4-Chlorophenyl)(4-formylphenyl)methyl]-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine

HRID 1058799Notes

Reaction equation

HRID 1058799 reaction equation
ClC1C=CC(C(C2C=CC(C=O)=CC=2)N2CC(=CS(CC3C=C(F)C=C(F)C=3)(=O)=O)C2)=CC=1.Cl.[Cl:35][C:36]1[CH:41]=[CH:40][C:39]([CH:42]([C:60]2[CH:65]=[CH:64][C:63]([CH:66]3OCC[O:67]3)=[CH:62][CH:61]=2)[N:43]2[CH2:46][C:45](=[C:47]([C:52]3[CH:57]=[C:56]([F:58])[CH:55]=[C:54]([F:59])[CH:53]=3)[S:48]([CH3:51])(=[O:50])=[O:49])[CH2:44]2)=[CH:38][CH:37]=1.[OH-].[Na+]>O1CCCC1.O.ClCCl>[Cl:35][C:36]1[CH:41]=[CH:40][C:39]([CH:42]([C:60]2[CH:61]=[CH:62][C:63]([CH:66]=[O:67])=[CH:64][CH:65]=2)[N:43]2[CH2:44][C:45](=[C:47]([C:52]3[CH:53]=[C:54]([F:59])[CH:55]=[C:56]([F:58])[CH:57]=3)[S:48]([CH3:51])(=[O:50])=[O:49])[CH2:46]2)=[CH:38][CH:37]=1

Participants

8

Reactant 4

HCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 22506743(+)-1-{(4-Chlorophenyl)[4-(1,3-dioxolan-2-yl)phenyl]methyl}-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]-azetidineHCID 86584737(-)-1-[(4-Chlorophenyl)(4-formylphenyl)methyl]-3-[(3,5-difluorophenyl)methylsulfonylmethylene]azetidine

Product 1

HCID 22506638(-)-1-[(4-Chlorophenyl)(4-formylphenyl)methyl]-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidineYield 105.1%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent

Procedure

(−)-1-[(4-Chlorophenyl)(4-formylphenyl)methyl]-3-[(3,5-difluorophenyl)methylsulfonylmethylene]azetidine may be prepared in the following manner: 3.32 cm3 of a 5 N solution of hydrochloric acid are poured into a solution of 0.83 g of (+)-1-{(4-chlorophenyl)[4-(1,3-dioxolan-2-yl)phenyl]methyl}-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine in 5 cm3 of tetrahydrofuran and then the mixture is kept stirring for 20 hours. Dichloromethane and water are added to the reaction medium followed by a 30% aqueous solution of sodium hydroxide until a pH=14 is obtained. The aqueous phase is extracted with dichloromethane, the organic phase is washed successively with water, with a saturated aqueous solution of sodium chloride, dried over magnesium sulfate, filtered and evaporated to dryness under reduced pressure (2.7 kpa). 0.8 g of (−)-1-[(4-chlorophenyl)(4-formylphenyl)methyl]-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine is obtained in the form of a white foam.

Workup

  1. customis obtained
  2. extractionThe aqueous phase is extracted with dichloromethane
  3. washthe organic phase is washed successively with water, with a saturated aqueous solution of sodium chloride
  4. dry with materialdried over magnesium sulfate
  5. filtrationfiltered
  6. customevaporated to dryness under reduced pressure (2.7 kpa)

Sources & evidence

ORD record
ord-e3c34b68a3774869ac8ffd01c66c025c
Source dataset
uspto-grants-2003_02
Patent number
US06518264B2

Reaction notes

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