Dichloromethane → (R)-(4-(chlorophenyl) [4-(di-n-propylaminomethyl)phenyl]methyl}-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine

HRID 25199Notes

Reaction equation

HRID 25199 reaction equation
Cl[CH2:2][C:3]1[CH:8]=[CH:7][C:6]([C@H:9](C2C=CC(Cl)=CC=2)[N:10]2[CH2:13][C:12](=[C:14]([C:19]3[CH:24]=[C:23]([F:25])[CH:22]=[C:21]([F:26])[CH:20]=3)[S:15]([CH3:18])(=[O:17])=[O:16])[CH2:11]2)=[CH:5][CH:4]=1.[CH2:34]([NH:37][CH2:38][CH2:39][CH3:40])[CH2:35][CH3:36].Cl[CH2:42][Cl:43]>>[Cl:43][C:42]1[CH:7]=[CH:8][CH:3]=[CH:4][C:5]=1[C@:3]1([CH2:2][N:37]([CH2:38][CH2:39][CH3:40])[CH2:34][CH2:35][CH3:36])[CH:8]=[CH:7][C:6]([CH2:9][N:10]2[CH2:13][C:12](=[C:14]([C:19]3[CH:20]=[C:21]([F:26])[CH:22]=[C:23]([F:25])[CH:24]=3)[S:15]([CH3:18])(=[O:16])=[O:17])[CH2:11]2)=[CH:5][CH2:4]1

Participants

4

Reactant 3

HCID 6344DichloromethaneHCID 8902DipropylamineHCID 685858541-{(R)-[4-(chloromethyl)phenyl](4-chlorophenyl)methyl}-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine

Product 1

HCID 86584741(R)-(4-(chlorophenyl) [4-(di-n-propylaminomethyl)phenyl]methyl}-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine

Procedure

The operation is carried out as described in Example 87, starting with 0.05 g of 1-{(R*)-[4-(chloromethyl)phenyl](4-chlorophenyl)methyl}-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine, form A isomer, 1.0 cm3 of dichloromethane, and 0.020 g of di-n-propylamine. The crude product is chromatographed on a silica gel column (particle size 0.06-0.200 mm, diameter 8 mm, height 8 cm), eluting with 80 cm3 of dichloromethane and then with a dichloromethane and methanol mixture (95/5 by volume), collecting 2.5 cm3 fractions immediately after using this eluent mixture. Fractions 3 to 8 are combined and then concentrated to dryness under reduced pressure (2.7 kPa). 0.025 g of 1-{(R*)-(4-(chlorophenyl)[4-(di-n-propylaminomethyl)phenyl]methyl}-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine, form A isomer, is obtained in the form of a white foam [1H NMR spectrum (400 MHz, CDCl3, δ in ppm): 0.85 (t, J=7 Hz, 6H) 1.45 (mt, 4H), 2.34 (t, J=7.5 Hz, 4H), 2.80 (s, 3H), 3.48 (s, 2H), 3.84 (mt, 2H), 4.33 (mt, 2H), 4.50 (s, 1H), 6.83 (tt, J=9 and 2.5 Hz, 1H), 6.98 (mt, 2H), from 7.20 to 7.40 (mt, 8H)].

Workup

  1. customThe crude product is chromatographed on a silica gel column (particle size 0.06-0.200 mm, diameter 8 mm, height 8 cm)
  2. washeluting with 80 cm3 of dichloromethane
  3. customwith a dichloromethane and methanol mixture (95/5 by volume), collecting 2.5 cm3 fractions immediately
  4. concentrationconcentrated to dryness under reduced pressure (2.7 kPa)

Sources & evidence

ORD record
ord-ef8ef87de1d64623bf3d2ff0c7bc8a26
Source dataset
uspto-grants-2005_02
Patent number
US06858603B2

Reaction notes

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