Methanesulfonyl chloride → 1-{(R)-[4-(chloromethyl)phenyl](4-chlorophenyl)methyl}-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine

HRID 1058810Notes

Reaction equation

HRID 1058810 reaction equation
[Cl:1][CH2:2][C:3]1[CH:8]=[CH:7][C:6]([C@H:9]([C:28]2[CH:33]=[CH:32][C:31]([Cl:34])=[CH:30][CH:29]=2)[N:10]2[CH2:13][C:12]([C@H:15]([C:20]3[CH:25]=[C:24]([F:26])[CH:23]=[C:22]([F:27])[CH:21]=3)[S:16]([CH3:19])(=[O:18])=[O:17])(O)[CH2:11]2)=[CH:5][CH:4]=1.CS(Cl)(=O)=O>CN(C)C1C=CN=CC=1.ClCCl>[Cl:1][CH2:2][C:3]1[CH:8]=[CH:7][C:6]([C@H:9]([C:28]2[CH:29]=[CH:30][C:31]([Cl:34])=[CH:32][CH:33]=2)[N:10]2[CH2:13][C:12](=[C:15]([C:20]3[CH:21]=[C:22]([F:27])[CH:23]=[C:24]([F:26])[CH:25]=3)[S:16]([CH3:19])(=[O:18])=[O:17])[CH2:11]2)=[CH:5][CH:4]=1

Participants

5

Reactant 2

HCID 31297Methanesulfonyl chlorideHCID 685864761-{(R*)-[4-(chloromethyl)phenyl](4-chlorophenyl)methyl}-3-[(S)-(3,5-difluorophenyl)(methylsulfonyl)methyl]azetidin-3-ol

Product 1

HCID 685858541-{(R)-[4-(chloromethyl)phenyl](4-chlorophenyl)methyl}-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolvent

Procedure

1-{(R*)-[4-(chloromethyl)phenyl](4-(chlorophenyl)methyl}-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine, form B isomer, may be prepared by carrying out the operation as described in Example 87, starting with 7.3 g of the mixture of the 2 diastereoisomers (B forms) 1-{(R*)-[4-(chloromethyl)phenyl](4-chlorophenyl)methyl}-3-[(R)-(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidin-3-ol and 1-{(R*)-[4-(chloromethyl)phenyl](4-chlorophenyl)methyl}-3-[(S)-(3,5-difluorophenyl)(methylsulfonyl)methyl]azetidin-3-ol, 8.2 g of 4-dimethylaminopyridine, 150 cm3 of dichloromethane and 3.2 cm3 of methanesulfonyl chloride. The crude product is chromatographed on a silica gel column (particle size 0.04-0.06 mm, diameter 3 cm, height 30 cm), at an argon pressure of 0.2 bar, eluting with dichloromethane and collecting 100 cm3 fractions. Fractions 15 to 30 are combined and then concentrated to dryness under reduced pressure (2.7 kPa). 2.50 g of 1-{(R*)-[4-(chloromethyl)phenyl]-(4-chlorophenyl)methyl}-3-{(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine, form B isomer, are obtained in the form of a white foam.

Workup

  1. customThe crude product is chromatographed on a silica gel column (particle size 0.04-0.06 mm, diameter 3 cm, height 30 cm), at an argon pressure of 0.2 bar
  2. washeluting with dichloromethane
  3. customcollecting 100 cm3 fractions
  4. concentrationconcentrated to dryness under reduced pressure (2.7 kPa)

Sources & evidence

ORD record
ord-df653e5f968341e29ae16e808542f53f
Source dataset
uspto-grants-2003_02
Patent number
US06518264B2

Reaction notes

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