Dimethylformamide → Bis-(2-chloroethyl){4-[5-(2-fluorobiphenyl-4-yl)-1,2,4-oxadiazole-3-yl]benzyl}amine

HRID 2407504Notes

Reaction equation

HRID 2407504 reaction equation
S(Cl)([Cl:3])=O.[F:5][C:6]1[CH:11]=[C:10]([C:12]2[O:16][N:15]=[C:14]([C:17]3[CH:30]=[CH:29][C:20]([CH2:21][N:22]([CH2:26]CO)[CH2:23][CH2:24]O)=[CH:19][CH:18]=3)[N:13]=2)[CH:9]=[CH:8][C:7]=1[C:31]1[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=1.CN(C)C=O.Cl[CH2:43][Cl:44]>>[Cl:3][CH2:24][CH2:23][N:22]([CH2:26][CH2:43][Cl:44])[CH2:21][C:20]1[CH:29]=[CH:30][C:17]([C:14]2[N:13]=[C:12]([C:10]3[CH:9]=[CH:8][C:7]([C:31]4[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=4)=[C:6]([F:5])[CH:11]=3)[O:16][N:15]=2)=[CH:18][CH:19]=1

Participants

5

Reactant 4

HCID 6228DimethylformamideHCID 6344DichloromethaneHCID 24386Thionyl ChlorideHCID 595094342-[{4-[5-(2-Fluorobiphenyl-4-yl)-1,2,4-oxadiazole-3-yl]benzyl}(2-hydroxyethyl)amino]ethanol

Product 1

HCID 59509478Bis-(2-chloroethyl){4-[5-(2-fluorobiphenyl-4-yl)-1,2,4-oxadiazole-3-yl]benzyl}amine

Conditions

Temperature
80 °C

Procedure

Thionyl chloride (52 mL, 0.716 mol) is added drop wise to a stirred solution of 2-[{4-[5-(2-fluoro-biphenyl-4-yl)-1,2,4-oxadiazole-3-yl]benzyl}(2-hydroxyethyl)-amino]ethanol (31 g, 0.0715 mol) in dichloromethane (150 mL) at 0° C. N,N-Dimethylformamide (2 mL) is added and the reaction mixture is heated at 80° C. for 1 h. Excess thionyl chloride is removed under reduced pressure and the residue is made alkaline (pH ˜9) by the addition of an aqueous sodium hydroxide solution (4N, 150 mL) at room temperature. The aqueous layer is extracted with ethyl acetate (2×100 mL) and combined organic layers are dried over sodium sulphate. Removal of solvent under reduced pressure gives a viscous liquid, which is purified by column chromatography (silica gel 230-400 mesh, n-hexane:ethyl acetate 7:3) to give bis-(2-chloroethyl){4-[5-(2-fluorobiphenyl-4-yl)-1,2,4-oxadiazole-3-yl]benzyl}amine.

Workup

  1. customExcess thionyl chloride is removed under reduced pressure
  2. additionby the addition of an aqueous sodium hydroxide solution (4N, 150 mL) at room temperature
  3. extractionThe aqueous layer is extracted with ethyl acetate (2×100 mL)
  4. dry with materialare dried over sodium sulphate
  5. customRemoval of solvent under reduced pressure
  6. customgives a viscous liquid, which
  7. customis purified by column chromatography (silica gel 230-400 mesh, n-hexane:ethyl acetate 7:3)

Sources & evidence

ORD record
ord-04285bb8b1ea4d02a11babda30274159
Source dataset
uspto-grants-2014_08
Patent number
US08809539B2

Reaction notes

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