Sodium Iodide → 3-[(3,5-Difluorophenyl)(methylsulfonyl)-methylene]azetidine

HRID 25196Notes

Reaction equation

N1CCCC1.ClCC1C=CC([C@H](C2C=CC(Cl)=CC=2)[N:15]2[CH2:18][C:17](=[C:19]([C:24]3[CH:29]=[C:28]([F:30])[CH:27]=[C:26]([F:31])[CH:25]=3)[S:20]([CH3:23])(=[O:22])=[O:21])[CH2:16]2)=CC=1.[I-].[Na+]>ClCCl>[F:31][C:26]1[CH:25]=[C:24]([C:19](=[C:17]2[CH2:18][NH:15][CH2:16]2)[S:20]([CH3:23])(=[O:22])=[O:21])[CH:29]=[C:28]([F:30])[CH:27]=1

Participants

Conditions

Temperature: 20 °C

Procedure

50 mm3 of pyrrolidine are added to a solution of 0.32 g of 1-{(R*)-[4-(chloromethyl)phenyl](4-chlorophenyl)methyl}-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine, form A isomer, and 5 mg of sodium iodide in 10 cm3 of dichloromethane. After stirring for 20 hours at 20° C., 50 mm3 of pyrrolidine are added to the mixture, stirred for 8 hours and then 50 mm3 of pyrrolidine are again added and the mixture is stirred for 20 hours at 20° C. The reaction mixture is washed with water and then the organic phase is dried over magnesium sulfate and concentrated to dryness under vacuum (2.7 kPa). The residue obtained is chromatographed on a silica gel column (particle size 0.06-0.200 mm, diameter 1.2 cm, height 30 cm), at an argon pressure of 0.1 bar, eluting with dichloromethane and then with a dichloromethane and methanol mixture (97.5/2.5 by volume) and collecting 3 cm3 fractions. Fractions 12 to 40 are combined and then concentrated to dryness under reduced pressure (2.7 kPa). 0.18 g of 1-{(R*)-(4-chlorophenyl)[4-pyrrolidinylmethyl)phenyl]methyl}-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine, form A isomer, is obtained in the form of a white foam [a]20365 nm=−22.5°+/−0.7 (c=0.5%; dichloromethane) [1H NMR spectrum (300 MHz, CDCl3, δ in ppm): 1.78 (mt, 4H), 2.51 (mt, 4H), 2.81 (s, 3H), 3.58 (s, 2H), 3.84 (mt, 2H), 4.33 (mt, 2H), 4.50 (s, 1H), 6.84 (tt, J=9 and 2.5 Hz, 1H), 6.98 (mt, 2H), from 7.20 to 7.40 (mt, 8H)].

Workup

stirringstirred for 8 hours
stirringthe mixture is stirred for 20 hours at 20° C
washThe reaction mixture is washed with water
dry with materialthe organic phase is dried over magnesium sulfate
concentrationconcentrated to dryness under vacuum (2.7 kPa)
customThe residue obtained
customis chromatographed on a silica gel column (particle size 0.06-0.200 mm, diameter 1.2 cm, height 30 cm), at an argon pressure of 0.1 bar
washeluting with dichloromethane
customwith a dichloromethane and methanol mixture (97.5/2.5 by volume) and collecting 3 cm3 fractions
concentrationconcentrated to dryness under reduced pressure (2.7 kPa)

Sources & evidence

ORD record: ord-9d9cc474182a4171924e8f21634afad3
Source dataset: uspto-grants-2005_02
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US06858603B2

Reaction notes

Loading…