Sodium Bicarbonate → 1-Benzoyl-3-[2-[4-[1-(4-fluoro-benzyl)-1 H-benzoimidazol-2-yl]-4-hydroxy-piperidin-1-yl]-ethyl]-3-(3,4-dimethoxy-phenyl)-pyrrolidine

HRID 2269839Notes

Reaction equation

HRID 2269839 reaction equation
[C:1]([N:9]1[CH2:13][CH2:12][C:11]([C:20]2[CH:25]=[CH:24][C:23]([O:26][CH3:27])=[C:22]([O:28][CH3:29])[CH:21]=2)([CH2:14][CH2:15]S(C)(=O)=O)[CH2:10]1)(=[O:8])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[F:30][C:31]1[CH:53]=[CH:52][C:34]([CH2:35][N:36]2[C:40]3[CH:41]=[CH:42][CH:43]=[CH:44][C:39]=3[N:38]=[C:37]2[C:45]2([OH:51])[CH2:50][CH2:49][NH:48][CH2:47][CH2:46]2)=[CH:33][CH:32]=1.C(=O)(O)[O-].[Na+].C(OCC)(=O)C.CO>O1CCCC1.O.ClCCl>[C:1]([N:9]1[CH2:13][CH2:12][C:11]([CH2:14][CH2:15][N:48]2[CH2:49][CH2:50][C:45]([C:37]3[N:36]([CH2:35][C:34]4[CH:52]=[CH:53][C:31]([F:30])=[CH:32][CH:33]=4)[C:40]4[CH:41]=[CH:42][CH:43]=[CH:44][C:39]=4[N:38]=3)([OH:51])[CH2:46][CH2:47]2)([C:20]2[CH:25]=[CH:24][C:23]([O:26][CH3:27])=[C:22]([O:28][CH3:29])[CH:21]=2)[CH2:10]1)(=[O:8])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

7

Reactant 4

HCID 516892Sodium BicarbonateHCID 155428841-Benzoyl-3-(3,4-dimethoxy-phenyl)-3-(2-methanesulfonyl-ethyl)-pyrrolidineHCID 155428854-(1-(4-fluorobenzyl)-1H-benzoimidazol-2-yl)-4-hydroxypiperidineHCID 21584119Ethylacetate methanol

Product 1

HCID 101463851-Benzoyl-3-[2-[4-[1-(4-fluoro-benzyl)-1 H-benzoimidazol-2-yl]-4-hydroxy-piperidin-1-yl]-ethyl]-3-(3,4-dimethoxy-phenyl)-pyrrolidine

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 21881883Oxolane--water (1/1)Solvent

Procedure

Combine 1-benzoyl-3-(3,4-dimethoxy-phenyl)-3-(2-methanesulfonyl-ethyl)-pyrrolidine (0.48 g, 1.1 mmol) and 4-[1-(4-fluoro-benzyl)-1 H-benzoimidazol-2-yl]-4-hydroxy-piperidine (0.54 g, 1.7 mmol), and sodium bicarbonate (0.235 g, 2.22 mmol) in tetrahydrofuran/water (15/4) (50 mL). Heat to reflux. After 72 hours, cool to ambient temperature and evaporate in vacuo to obtain a residue. Partition the residue between dichloromethane and 5% sodium bicarbonate solution. Dry the organic layer over Na2SO4, filter, and concentrate in vacuo to obtain a residue. Chromatograph the residue on silica gel eluting with 5/1 ethyl acetate/methanol to give a solid. Combine the solid with dichloromethane and extract with 5% sodium bicarbonate solution. Dry the organic layer over Na2SO4, filter, and concentrate in vacuo to obtain a solid residue. Dry the residue in vacuo at 82° C. to give the title compound: Rf=0.32 (silica gel, 5/1 ethyl acetate/methanol); mp; 111-114° C. HRMS (FAB+): calculated 663.334502. Found 663.334660.

Workup

  1. temperatureHeat to reflux
  2. customevaporate in vacuo
  3. customto obtain a residue
  4. customPartition the residue between dichloromethane and 5% sodium bicarbonate solution
  5. dry with materialDry the organic layer over Na2SO4
  6. filtrationfilter
  7. concentrationconcentrate in vacuo
  8. customto obtain a residue
  9. extractionextract with 5% sodium bicarbonate solution
  10. dry with materialDry the organic layer over Na2SO4
  11. filtrationfilter
  12. concentrationconcentrate in vacuo
  13. customto obtain a solid residue
  14. customDry the residue in vacuo at 82° C.

Sources & evidence

ORD record
ord-639b930d7f744d17944c15b0c54450f9
Source dataset
uspto-grants-2001_12
Patent number
US06329392B1

Reaction notes

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