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

HRID 25204ノート

反応式

HRID 25204 の反応式
[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

参加物

5

反応物 2

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

生成物 1

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

試薬・触媒・溶媒 2

HCID 142844-(Dimethylamino)pyridine触媒HCID 6344Dichloromethane溶媒

実験手順

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.

後処理

  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)

出典と根拠

ORDレコード
ord-e16697da95b747b2a75f3b288d7ec47f
出典データセット
uspto-grants-2005_02
特許番号
US06858603B2

反応ノート

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