N-bromobutanimide → Tert-butyl 2-{2-[6-bromo-3-(2,2-dimethylpropionylamino)-2-methoxycarbonylphenyl]-ethyl}-pyrrolidine-1-carboxylate

HRID 715970Notes

Reaction equation

HRID 715970 reaction equation
[Br:1]N1C(=O)CCC1=O.[CH3:9][C:10]([CH3:39])([CH3:38])[C:11]([NH:13][C:14]1[C:15]([C:34]([O:36][CH3:37])=[O:35])=[C:16]([CH2:20][CH2:21][CH:22]2[CH2:26][CH2:25][CH2:24][N:23]2[C:27]([O:29][C:30]([CH3:33])([CH3:32])[CH3:31])=[O:28])[CH:17]=[CH:18][CH:19]=1)=[O:12]>C(#N)C>[Br:1][C:17]1[C:16]([CH2:20][CH2:21][CH:22]2[CH2:26][CH2:25][CH2:24][N:23]2[C:27]([O:29][C:30]([CH3:31])([CH3:32])[CH3:33])=[O:28])=[C:15]([C:34]([O:36][CH3:37])=[O:35])[C:14]([NH:13][C:11](=[O:12])[C:10]([CH3:39])([CH3:38])[CH3:9])=[CH:19][CH:18]=1

Participants

4

Reactant 2

HCID 67184N-bromobutanimideHCID 70984356Tert-butyl 2-{2-[3-(2,2-dimethylpropionylamino)-2-methoxycarbonyl-phenyl]-ethyl}-pyrrolidine-1-carboxylate2×

Product 1

HCID 70982387Tert-butyl 2-{2-[6-bromo-3-(2,2-dimethylpropionylamino)-2-methoxycarbonylphenyl]-ethyl}-pyrrolidine-1-carboxylateYield 78.7%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

N-Bromosuccinimide (1.24 g) was added to a solution of tert butyl 2-{2-[3-(2,2-dimethyl-propionylamino)-2-methoxycarbonylphenyl]-ethyl}-pyrrolidine-1-carboxylate (Intermediate 37, 2.74 g) in acetonitrile (40 mL) and the resultant mixture was stirred for 1 hour at room temperature. The mixture was concentrated in vacuo and the residue was partitioned between ethyl acetate and water. The organic layer was dried (Na2SO4) and filtered and the filtrate was concentrated in vacuo. The residue was purified by chromatography on silica, eluting with a mixture of ethyl acetate and cyclohexane with a gradient of 0-25% to give tert butyl 2-{2-[6-bromo-3-(2,2-dimethylpropionylamino)-2-methoxycarbonylphenyl]-ethyl}-pyrrolidine-1-carboxylate (2.55 g) as a colourless gum.

Workup

  1. concentrationThe mixture was concentrated in vacuo
  2. customthe residue was partitioned between ethyl acetate and water
  3. dry with materialThe organic layer was dried (Na2SO4)
  4. filtrationfiltered
  5. concentrationthe filtrate was concentrated in vacuo
  6. customThe residue was purified by chromatography on silica
  7. washeluting with a mixture of ethyl acetate and cyclohexane with a gradient of 0-25%

Sources & evidence

ORD record
ord-2a727defd0414013b3aa24abdc6a35c3
Source dataset
uspto-grants-2015_11
Patent number
US09187494B2

Reaction notes

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