Dichloromethane → di-tert-butyl (2S,2'S)-2,2'-{[2-(4-tert-butylphenyl)-1H-pyrrole-1,3-diyl]bis(benzene-4,1-diyl-1H-imidazole-4,2-diyl)}dipyrrolidine-1-carboxylate

HRID 1411445Notes

Reaction equation

HRID 1411445 reaction equation
[C:1]([C:5]1[CH:10]=[CH:9][C:8]([C:11]2[N:12]([C:31]3[CH:36]=[CH:35][C:34](B4OC(C)(C)C(C)(C)O4)=[CH:33][CH:32]=3)[CH:13]=[CH:14][C:15]=2[C:16]2[CH:21]=[CH:20][C:19](B3OC(C)(C)C(C)(C)O3)=[CH:18][CH:17]=2)=[CH:7][CH:6]=1)([CH3:4])([CH3:3])[CH3:2].Br[C:47]1[NH:51][C:50]([C@@H:52]2[CH2:56][CH2:55][CH2:54][N:53]2[C:57]([O:59][C:60]([CH3:63])([CH3:62])[CH3:61])=[O:58])=[N:49][CH:48]=1.ClCCl.[C:67](=[O:70])([O-])[O-:68].[Na+].[Na+]>C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2].O.C1(C)C=CC=CC=1.C(O)C>[C:1]([C:5]1[CH:10]=[CH:9][C:8]([C:11]2[N:12]([C:31]3[CH:36]=[CH:35][C:34]([C:47]4[N:51]=[C:50]([C@@H:52]5[CH2:56][CH2:55][CH2:54][N:53]5[C:67]([O:68][C:60]([CH3:63])([CH3:62])[CH3:61])=[O:70])[NH:49][CH:48]=4)=[CH:33][CH:32]=3)[CH:13]=[CH:14][C:15]=2[C:16]2[CH:17]=[CH:18][C:19]([C:47]3[N:51]=[C:50]([C@@H:52]4[CH2:56][CH2:55][CH2:54][N:53]4[C:57]([O:59][C:60]([CH3:63])([CH3:62])[CH3:61])=[O:58])[NH:49][CH:48]=3)=[CH:20][CH:21]=2)=[CH:7][CH:6]=1)([CH3:2])([CH3:4])[CH3:3]

Participants

9

Reactant 4

HCID 6344DichloromethaneHCID 10340Sodium CarbonateHCID 56605192tert-Butyl (2S)-2-(5-bromo-1H-imidazol-2-yl)pyrrolidine-1-carboxylateHCID 582268432-(4-tert-butylphenyl)-1,3-bis(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)-1H-pyrrole

Product 1

HCID 178451924di-tert-butyl (2S,2'S)-2,2'-{[2-(4-tert-butylphenyl)-1H-pyrrole-1,3-diyl]bis(benzene-4,1-diyl-1H-imidazole-4,2-diyl)}dipyrrolidine-1-carboxylateYield 9%

Reagents, catalysts & solvents 4

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 702EthanolSolventHCID 962WaterSolventHCID 1140TolueneSolvent

Procedure

The product from Example 7.1E (227 mg, 0.376 mmol), (S)-tert-butyl 2-(5-bromo-1H-imidazol-2-yl)pyrrolidine-1-carboxylate or (S)-tert-butyl 2-(4-bromo-1H-imidazol-2-yl)pyrrolidine-1-carboxylate (357 mg, 1.13 mmol), [1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium(II), complex with dichloromethane (27.5 mg, 0.038 mmol), and a solution of sodium carbonate (1.0 M in water, 1.13 mL, 1.13 mmol) were heated in a solution of ethanol (3 mL) and toluene (3 mL) at 85° C. for 18 hours. The mixture then had water (10 mL) added followed by extraction with EtOAc (2×10 mL). The organic extract was dried, filtered and concentrated, and then the residue was purified by chromatography (silica gel, methanol in dichloromethane) which afforded 29 mg, (9%) of the title compound; MS (ESI) m/z 823 (M+H)+.

Workup

  1. additionadded
  2. extractionfollowed by extraction with EtOAc (2×10 mL)
  3. extractionThe organic extract
  4. customwas dried
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customthe residue was purified by chromatography (silica gel, methanol in dichloromethane) which

Sources & evidence

ORD record
ord-ab55017d61b648968d6e72ce6368be17
Source dataset
uspto-grants-2014_12
Patent number
US08921514B2

Reaction notes

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