Water → 2-Pentafluoroethyl-5-fluoro-1-{1-[3-(4-fluoro-phenylsulfanyl)-propyl]-piperidin-4-yl}-1h-benzoimidazole

HRID 1371506Notes

Reaction equation

HRID 1371506 reaction equation
[NH:1]1[CH2:6][CH2:5][CH:4]([N:7]2[C:11]3[CH:12]=[CH:13][C:14]([F:16])=[CH:15][C:10]=3[N:9]=[C:8]2[C:17]([F:23])([F:22])[C:18]([F:21])([F:20])[F:19])[CH2:3][CH2:2]1.Br[CH2:25][CH2:26][CH2:27][S:28][C:29]1[CH:34]=[CH:33][C:32]([F:35])=[CH:31][CH:30]=1.C([O-])([O-])=O.[K+].[K+].O>CN(C=O)C>[F:22][C:17]([F:23])([C:8]1[N:7]([CH:4]2[CH2:5][CH2:6][N:1]([CH2:25][CH2:26][CH2:27][S:28][C:29]3[CH:34]=[CH:33][C:32]([F:35])=[CH:31][CH:30]=3)[CH2:2][CH2:3]2)[C:11]2[CH:12]=[CH:13][C:14]([F:16])=[CH:15][C:10]=2[N:9]=1)[C:18]([F:21])([F:20])[F:19]

Participants

6

Reactant 4

HCID 962WaterHCID 11430Potassium CarbonateHCID 14575314Benzene, 1-[(3-bromopropyl)thio]-4-fluoro-HCID 179896551-(Piperidin-4-yl)-5-fluoro-2-pentafluoroethyl-1 H-benzoimidazole

Product 1

HCID 179896562-Pentafluoroethyl-5-fluoro-1-{1-[3-(4-fluoro-phenylsulfanyl)-propyl]-piperidin-4-yl}-1h-benzoimidazoleYield 8.6%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

3.9 g 1-(Piperidin-4-yl)-5-fluoro-2-pentafluoroethyl-1H-benzoimidazole, 4.4 g 1-(3-bromo-propylsulfanyl)-4-fluoro-benzene and 2 g K2CO3 were stirred in 50 ml DMF at 100° C. for 2 h. After cooling the mixture was poured into water and was extracted 2× with ethyl acetate. The organic layer was tracted 3× with water, dried and evaporated. The resulting oil was purified by flash chromatography with dichloromethane, the purified fractions were dissolved in acetone after evaporation of the solvent, and the solution was acidified with etherical HCl. After evaporation of the solvent the resulting crystals were filtered with diisopropyl ether. The crystals were dissolved in acetone again and evaporated to a volume of 2 ml. The product crystallized as hydrochloride to give 0.5 g product (mp. 208–209° C.).

Workup

  1. temperatureAfter cooling the mixture
  2. extractionwas extracted 2× with ethyl acetate
  3. customdried
  4. customevaporated
  5. customThe resulting oil was purified by flash chromatography with dichloromethane
  6. dissolutionthe purified fractions were dissolved in acetone
  7. customafter evaporation of the solvent
  8. customAfter evaporation of the solvent the resulting crystals
  9. filtrationwere filtered with diisopropyl ether
  10. dissolutionThe crystals were dissolved in acetone again
  11. customevaporated to a volume of 2 ml
  12. customThe product crystallized as hydrochloride

Sources & evidence

ORD record
ord-335cd671a8704912a63ee9a1a038dcb1
Source dataset
uspto-grants-2007_01
Patent number
US07157471B2

Reaction notes

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