1,3-Dibromo-5,5-dimethylhydantoin → tert-Butyl (4-bromo-2-cyano-1H-pyrrol-1-yl)carbamate

HRID 1972709Notes

Reaction equation

HRID 1972709 reaction equation
C(=O)=O.C(#N)C.[C:7]([C:9]1[N:10]([NH:14][C:15](=[O:21])[O:16][C:17]([CH3:20])([CH3:19])[CH3:18])[CH:11]=[CH:12][CH:13]=1)#[N:8].[Br:22]N1C(C)(C)C(=O)N(Br)C1=O>C(#N)C.CCOC(C)=O>[Br:22][C:12]1[CH:13]=[C:9]([C:7]#[N:8])[N:10]([NH:14][C:15](=[O:21])[O:16][C:17]([CH3:18])([CH3:20])[CH3:19])[CH:11]=1

Participants

6

Reactant 3

HCID 64791,3-Dibromo-5,5-dimethylhydantoin2×HCID 50999066tert-butyl (2-cyano-1H-pyrrol-1-yl)carbamateHCID 86587134Acetonitrile dry ice

Product 1

HCID 57955231tert-Butyl (4-bromo-2-cyano-1H-pyrrol-1-yl)carbamate

Reagents, catalysts & solvents 2

HCID 6342AcetonitrileSolventHCID 8857Ethyl AcetateSolvent

Procedure

A 1 L, 3-neck RB flask was fitted with a mechanical stirrer, nitrogen inlet, thermocouple and thermocontroller, and dry-ice acetonitrile cooling. 2-Cyano-pyrrol-1-yl-carbamic acid, tert-butyl ester (20 g, 96.5 mmol) was added and dissolved in 350 mL acetonitrile and cooled to below −30° C. 1,3-Dibromo-5,5-dimethylhydantoin (13.79 g, 48.26 mmol) was added as a solid, and the reaction was allowed to warm to rt over 2 h. Analysis by RP-HPLC at 2 h indicated that about 10% starting material remained. The reaction was cooled again to below −30° C. and treated with additional 1,3-dibromo-5,5-dimethylhydantoin (1.3 g, 4.8 mmol). The reaction was allowed to warm slowly to rt over 3 h. The reaction was diluted with 500 mL EtOAc and transferred to a separatory funnel. The organic layer was washed with 1N aq sodium carbonate, water and brine and then dried with sodium sulfate. Filtration of the organic layer through silica gel removed much of the colored impurities. Evaporation of the solvent under vacuum provided reddish oil, which provided orange-brown crystals of the desired product upon seeding (27.16 g, 98%). 1H-NMR (DMSO): δ 10.95 (bs, 1H), 7.61 (d, 1H, J=2.0 Hz), 7.16 (d, 1H, J=2 Hz), 1.44 (s, 9H, J=4.4, 1.7 Hz). MS: LC/MS (+esi), m/z=[M+H].

Workup

  1. customA 1 L, 3-neck RB flask was fitted with a mechanical stirrer, nitrogen inlet
  2. temperaturecooled to below −30° C
  3. temperatureThe reaction was cooled again to below −30° C.
  4. temperatureto warm slowly to rt over 3 h
  5. customtransferred to a separatory funnel
  6. washThe organic layer was washed with 1N aq sodium carbonate, water and brine
  7. dry with materialdried with sodium sulfate
  8. filtrationFiltration of the organic layer through silica gel
  9. customremoved much of the colored impurities
  10. customEvaporation of the solvent under vacuum
  11. customprovided reddish oil, which

Sources & evidence

ORD record
ord-4412881e68ec4ddfaefcfeb41db8fc10
Source dataset
uspto-grants-2013_04
Patent number
US08431695B2

Reaction notes

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