1-Methylpiperazine → 1-{(R)-(4-chlorophenyl) [4-(4-methylpiperazin-1-ylmethyl)phenyl]methyl}-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine

Participants

Reaction Steps

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 N-methylpiperazine. 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 9 are combined and then concentrated to dryness under reduced pressure (2.7 kPa). 0.025 g of 1-{(R*)-(4-chlorophenyl)[4-(4-methylpiperazin-1-ylmethyl)phenyl]methyl}-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine, form A isomer, is obtained in the form of a white foam [1H NMR spectrum (300 MHz, CDCl3, δ in ppm): 2.28 (s, 3H), from 2.30 to 2.60 (unresolved complex, 8H), 2.80 (s, 3H), 3.45 (s, 2H), 3.84 (mt, 2H), 4.33 (mt, 2H), 4.50 (s, 1H), 6.84 (tt, J=8.5 and 2.5 Hz, 1H), 6.98 (mt, 2H), from 7.20 to 7.40 (mt, 8H)].

Provenance & Evidence