Pyrrolidine → HCID 71523248, compound

HRID 2178530Notes

Reaction equation

HRID 2178530 reaction equation
[O:1]=[C:2]1[CH2:7][CH2:6][CH2:5][CH2:4][N:3]1[C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][C:9]=1[CH2:14][CH2:15][N:16]1[CH2:20][CH2:19][CH:18]([C:21]2[CH:29]=[CH:28][CH:27]=[CH:26][C:22]=2[C:23]([OH:25])=O)[CH2:17]1.[NH:30]1[CH2:34][CH2:33][CH2:32][CH2:31]1.CN([P+](ON1N=NC2C=CC=CC1=2)(N(C)C)N(C)C)C.F[P-](F)(F)(F)(F)F>ClCCl>[N:30]1([C:23]([C:22]2[CH:26]=[CH:27][CH:28]=[CH:29][C:21]=2[CH:18]2[CH2:19][CH2:20][N:16]([CH2:15][CH2:14][C:9]3[CH:10]=[CH:11][CH:12]=[CH:13][C:8]=3[N:3]3[CH2:4][CH2:5][CH2:6][CH2:7][C:2]3=[O:1])[CH2:17]2)=[O:25])[CH2:34][CH2:33][CH2:32][CH2:31]1

Participants

5

Reactant 3

HCID 31268PyrrolidineHCID 151348Benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphateHCID 89500788HCID 89500788, compound

Product 1

HCID 71523248HCID 71523248, compoundYield 12%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

2-(1-{2-[2-(2-oxopiperidin-1-yl)phenyl]ethyl}pyrrolidin-3-yl)benzoic acid enantiomer 2 a6-8 (2.72 g, 6.97 mmol, 1 eq) is dissolved in dichloromethane (100 ml). Pyrrolidine (0.69 ml, 8.36 mmol, 1.2 eq) is added followed by BOP reagent (Benzotriazole-1-yl-oxy-tris-(dimethylamino)-phosphonium hexafluorophosphate; 4.62 g, 10.45 mmol, 1.5 eq) and the reaction mixture is stirred at room temperature for 4 h. The mixture is evaporated to dryness, redissolved in dichloromethane and the organic layer is washed with HCl 1N and water, dried over MgSO4 and evaporated. The residue is purified by reverse phase HPLC (gradient: acetonitrile/H2O/ammonium formate from 5% to 95% of acetonitrile in 8 minutes) to afford 385 mg of (−)-1-[2-(2-{3-[2-(pyrrolidin-1-ylcarbonyl)phenyl]pyrrolidin-1-yl}ethyl)phenyl]piperidin-2-one 17.

Workup

  1. customThe mixture is evaporated to dryness
  2. dissolutionredissolved in dichloromethane
  3. washthe organic layer is washed with HCl 1N and water
  4. dry with materialdried over MgSO4
  5. customevaporated
  6. customThe residue is purified by reverse phase HPLC (gradient: acetonitrile/H2O/ammonium formate from 5% to 95% of acetonitrile in 8 minutes)

Sources & evidence

ORD record
ord-c2b031dd0fef42a2a919d8e113725db2
Source dataset
uspto-grants-2015_06
Patent number
US09067930B2

Reaction notes

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