Methyl iodide → N-{1-[bis(4-chlorophenyl)methyl]azetidin-3-yl}-N-methyl-4-fluorophenylsulfonamide

HRID 1581923Notes

Reaction equation

HRID 1581923 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]([C:24]2[CH:29]=[CH:28][C:27]([Cl:30])=[CH:26][CH:25]=2)[N:9]2[CH2:12][CH:11]([NH:13][S:14]([C:17]3[CH:22]=[CH:21][C:20]([F:23])=[CH:19][CH:18]=3)(=[O:16])=[O:15])[CH2:10]2)=[CH:4][CH:3]=1.[H-].[Na+].IC.[C:35](OCC)(=O)C>O1CCCC1.O>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([CH:8]([C:24]2[CH:29]=[CH:28][C:27]([Cl:30])=[CH:26][CH:25]=2)[N:9]2[CH2:10][CH:11]([N:13]([CH3:35])[S:14]([C:17]3[CH:22]=[CH:21][C:20]([F:23])=[CH:19][CH:18]=3)(=[O:15])=[O:16])[CH2:12]2)=[CH:6][CH:7]=1

Participants

7

Reactant 4

HCID 6328Methyl iodideHCID 8857Ethyl AcetateHCID 24758Sodium hydrideHCID 10298542N-(1-[bis(4-chlorophenyl)methyl]azetidin-3-yl}-4-fluorophenylsulfonamide

Product 1

HCID 15521566N-{1-[bis(4-chlorophenyl)methyl]azetidin-3-yl}-N-methyl-4-fluorophenylsulfonamide

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
20 °C

Procedure

A solution of 0.26 g of N-{1-[bis(4-chlorophenyl)methyl]azetidin-3-yl}-4-fluorophenylsulfonamide in 5 cm3 of tetrahydrofuran is added, at room temperature under an argon atmosphere, to a suspension of 20.5 mg of 80% sodium hydride in 10 cm3 of tetrahydrofuran. After stirring for 1 hour at around 20° C., 60 mm3 of iodomethane are added and then after stirring for an additional 16 hours, the suspension is supplemented with 30 cm3 of ethyl acetate and 20 cm3 of distilled water. The organic phase is dried over magnesium sulfate, filtered and concentrated to dryness under reduced pressure (2.7 kPa). The residue is purified by flash chromatography on silica gel [eluant: cyclohexane/ethyl acetate (90/10 by volume)]. 19 mg of N-{1-[bis(4-chlorophenyl)methyl]azetidin-3-yl}-N-methyl-4-fluorophenylsulfonamide are thus obtained in the form of a white powder [1H NMR spectrum (300 MHz, CDCl3, δ in ppm): 2.69 (s: 3H); 3.02 (split t, J=7 and 2 Hz: 2H); 3.35 (split t, J=7 and 2 Hz: 2H); 3.91 (mt: 1H); 4.27 (s: 1H); from 7.15 to 7.35 (mt: 10H); 7.75 (dd, J=9 and 5 Hz: 2H)].

Workup

  1. stirringafter stirring for an additional 16 hours
  2. dry with materialThe organic phase is dried over magnesium sulfate
  3. filtrationfiltered
  4. concentrationconcentrated to dryness under reduced pressure (2.7 kPa)
  5. customThe residue is purified by flash chromatography on silica gel [eluant: cyclohexane/ethyl acetate (90/10 by volume)]

Sources & evidence

ORD record
ord-858579c5941c483e940173f9eb662846
Source dataset
uspto-grants-2004_05
Patent number
US06734176B2

Reaction notes

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