Piperidine → (S)-5-(4-bromophenyl)-2-(2-methylpyrrolidin-2-yl)-1H-imidazole

HRID 80377Notes

Reaction equation

HRID 80377 reaction equation
[Br:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[NH:12][C:11]([C@:13]3([CH3:35])[CH2:17][CH2:16][CH2:15][N:14]3C(OCC3C4C=CC=CC=4C4C3=CC=CC=4)=O)=[N:10][CH:9]=2)=[CH:4][CH:3]=1.N1CCCCC1>CN(C=O)C>[Br:1][C:2]1[CH:3]=[CH:4][C:5]([C:8]2[NH:12][C:11]([C@:13]3([CH3:35])[CH2:17][CH2:16][CH2:15][NH:14]3)=[N:10][CH:9]=2)=[CH:6][CH:7]=1

Participants

4

Reactant 2

HCID 8082PiperidineHCID 67460873(S)-(9H-fluoren-9-yl)methyl 2-(5-(4-bromophenyl)-1H-imidazol-2-yl)-2-methylpyrrolidine-1-carboxylate

Product 1

HCID 67460500(S)-5-(4-bromophenyl)-2-(2-methylpyrrolidin-2-yl)-1H-imidazoleYield 101.7%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To (S)-(9H-fluoren-9-yl)methyl 2-(5-(4-bromophenyl)-1H-imidazol-2-yl)-2-methylpyrrolidine-1-carboxylate (intermediate LS32; 329 mg; 0.62 mmol) in 3 mL DMF was added 1.5 mL piperidine. The reaction mixture was concentrated via a nitrogen stream overnite. The resultant residue was washed with hexane and passed through an MCX cartridge (Oasis; 6 g; preconditioned with two column lengths of methanol). The cartridge was washed with two column lengths of methanol and product was eluted with ammonia/methanol. Concentration provided 193 mg of (S)-5-(4-bromophenyl)-2-(2-methylpyrrolidin-2-yl)-1H-imidazole which was dissolved in 6 mL dichloromethane and combined with di-t-butyldicarbonate (413 mg; 1.89 mmol), DMAP (15 mg; 0.13 mmol) and TEA (0.17 mL; 1.30 mmol). After 48 h, the reaction mixture was concentrated and purified via chromatography on a Biotage system providing (S)-tert-butyl 5-(4-bromophenyl)-2-(1-(tert-butoxycarbonyl)-2-methylpyrrolidin-2-yl)-1H-imidazole-1-carboxylate (intermediate LS33; 150 mg; 48%) as an off white solid. LC (Cond'n 5): RT=3.75 min; MS: Anal. Calcd. for [M+H]+ C24H32BrN3O4: 506.2; found 506.4

Workup

  1. concentrationThe reaction mixture was concentrated via a nitrogen stream overnite
  2. washThe resultant residue was washed with hexane
  3. washThe cartridge was washed with two column lengths of methanol and product
  4. washwas eluted with ammonia/methanol
  5. concentrationConcentration

Sources & evidence

ORD record
ord-1a86a45ac4ce4d71ac002d7007bd8d29
Source dataset
uspto-grants-2014_09
Patent number
US08846023B2

Reaction notes

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