Potassium Carbonate → 1-(3,4,5-Trimethoxy-benzoyl)-3-[2-[4-[1-(4-fluoro-benzyl)-1 H-benzoimidazol-2-yl]-4-hydroxy-piperidin-1-yl]-ethyl]-3-(3,4-dichloro-phenyl)-pyrrolidine

HRID 2269846Notes

Reaction equation

HRID 2269846 reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[C:5]([CH:27]=[C:28]([O:32][CH3:33])[C:29]=1[O:30][CH3:31])[C:6]([N:8]1[CH2:12][CH2:11][C:10]([C:19]2[CH:24]=[CH:23][C:22]([Cl:25])=[C:21]([Cl:26])[CH:20]=2)([CH2:13][CH2:14]S(C)(=O)=O)[CH2:9]1)=[O:7].[F:34][C:35]1[CH:57]=[CH:56][C:38]([CH2:39][N:40]2[C:44]3[CH:45]=[CH:46][CH:47]=[CH:48][C:43]=3[N:42]=[C:41]2[C:49]2([OH:55])[CH2:54][CH2:53][NH:52][CH2:51][CH2:50]2)=[CH:37][CH:36]=1.C(=O)([O-])[O-].[K+].[K+].C(OCC)(=O)C.CO>O1CCCC1.O>[CH3:1][O:2][C:3]1[CH:4]=[C:5]([CH:27]=[C:28]([O:32][CH3:33])[C:29]=1[O:30][CH3:31])[C:6]([N:8]1[CH2:12][CH2:11][C:10]([CH2:13][CH2:14][N:52]2[CH2:53][CH2:54][C:49]([C:41]3[N:40]([CH2:39][C:38]4[CH:56]=[CH:57][C:35]([F:34])=[CH:36][CH:37]=4)[C:44]4[CH:45]=[CH:46][CH:47]=[CH:48][C:43]=4[N:42]=3)([OH:55])[CH2:50][CH2:51]2)([C:19]2[CH:24]=[CH:23][C:22]([Cl:25])=[C:21]([Cl:26])[CH:20]=2)[CH2:9]1)=[O:7]

Participants

6

Reactant 4

HCID 11430Potassium CarbonateHCID 155428854-(1-(4-fluorobenzyl)-1H-benzoimidazol-2-yl)-4-hydroxypiperidineHCID 155428861-(3,4,5-Trimethoxy-benzoyl)-3-(3,4-dichloro-phenyl)-3-(2-methanesulfonyl-ethyl)-pyrrolidineHCID 21584119Ethylacetate methanol2×

Product 1

HCID 155428651-(3,4,5-Trimethoxy-benzoyl)-3-[2-[4-[1-(4-fluoro-benzyl)-1 H-benzoimidazol-2-yl]-4-hydroxy-piperidin-1-yl]-ethyl]-3-(3,4-dichloro-phenyl)-pyrrolidine

Reagents, catalysts & solvents 1

HCID 21881883Oxolane--water (1/1)Solvent

Procedure

Combine 1-(3,4,5-trimethoxy-benzoyl)-3-(3,4-dichloro-phenyl)-3-(2-methanesulfonyl-ethyl)-pyrrolidine (0.20 g, 0.38 mmol) and 4-[1-(4-fluoro-benzyl)-1 H-benzoimidazol-2-yl]-4-hydroxy-piperidine (0.15 g, 0.46 mmol), and potassium carbonate (0.16 g, 1.13 mmol) in tetrahydrofuran/water (3/1) (40 mL). Heat to reflux. After 6 days, cool and evaporate in vacuo to obtain a residue. Partition the residue between dichloromethane and water. Extract the organic layer with 1 M hydrochloric acid solution, a 5% sodium bicarbonate solution, and water. Dry the organic layer over Na2SO4, filter, and concentrate in vacuo to obtain a residue. Chromatograph the residue on silica gel eluting sequentially with 10/1 ethyl acetate/methanol and 2/1 ethyl acetate/methanol to give the title compound: Rf=0.57 (silica gel, 2/1 ethyl acetate/methanol).

Workup

  1. temperatureHeat to reflux
  2. temperaturecool
  3. customevaporate in vacuo
  4. customto obtain a residue
  5. customPartition the residue between dichloromethane and water
  6. extractionExtract the organic layer with 1 M hydrochloric acid solution
  7. dry with materialDry the organic layer over Na2SO4
  8. filtrationfilter
  9. concentrationconcentrate in vacuo
  10. customto obtain a residue

Sources & evidence

ORD record
ord-bed5807c2e4b44e18c9aee3ef18c0091
Source dataset
uspto-grants-2001_12
Patent number
US06329392B1

Reaction notes

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