1,3-Dibromo-5,5-dimethylhydantoin → tert-butyl N-[6-(bromomethyl)-2-pyridyl]-N-tert-butoxycarbonyl-carbamate

HRID 2363801Notes

Reaction equation

HRID 2363801 reaction equation
[C:1]([O:5][C:6]([N:8]([C:16]1[CH:21]=[CH:20][CH:19]=[C:18]([CH3:22])[N:17]=1)[C:9](=[O:15])[O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[O:7])([CH3:4])([CH3:3])[CH3:2].N(C(C)(C)C#N)=NC(C)(C)C#N.[Br:35]N1C(C)(C)C(=O)N(Br)C1=O>ClC1C=CC=CC=1>[C:1]([O:5][C:6]([N:8]([C:9]([O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[O:15])[C:16]1[CH:21]=[CH:20][CH:19]=[C:18]([CH2:22][Br:35])[N:17]=1)=[O:7])([CH3:2])([CH3:3])[CH3:4]

Participants

5

Reactant 3

HCID 64791,3-Dibromo-5,5-dimethylhydantoinHCID 6547AzobisisobutyronitrileHCID 59139130tert-Butyl N-[(tert-butoxy)carbonyl]-N-(6-methylpyridin-2-yl)carbamate

Product 1

HCID 59139156tert-butyl N-[6-(bromomethyl)-2-pyridyl]-N-tert-butoxycarbonyl-carbamate

Reagents, catalysts & solvents 1

HCID 7964ChlorobenzeneSolvent

Conditions

Temperature
90 °C

Procedure

To 102.8 g (334 mmol) of t-butyl t-butoxycarbonyl-(6-methyl-pyridin-2-yl)-carbamate were added 10.95 g (20 mol %) of 2,2′-azobisisobutyronitrile and 1,330 ml of chlorobenzene. To the resulting mixture was added 95.31 g of 1,3-dibromo-5,5-dimethylhydantoin, and the temperature of the mixture was then raised to 90° C. at a rate of 2° C./minute and held at the temperature for one hour. Subsequently, the reaction mixture was cooled to 20° C., the precipitate was filtered off, and the volume of chlorobenzene was reduced by half by distillation. The thus obtained residue was cooled to 10° C. or lower, and then 46.03 g (43 ml) of diisopropylethylamine and 43.08 g (58 ml) of diethyl phosphite were added thereto, followed by aging the mixture at room temperature for 16.5 hours. Following confirmation by performing thin-layer chromatography that the raw materials had disappeared, the reaction mixture was washed with 300 ml of 3 N hydrochloric acid, and then further washed with 500 ml of a saturated saline solution. The resulting solution was then dried over anhydrous magnesium sulfate and filtered, yielding a solution of 2-bis(t-butoxycarbonyl)amino-6-bromomethyl-pyridine.

Workup

  1. temperatureSubsequently, the reaction mixture was cooled to 20° C.
  2. filtrationthe precipitate was filtered off
  3. distillationthe volume of chlorobenzene was reduced by half by distillation
  4. temperatureThe thus obtained residue was cooled to 10° C.
  5. additionlower, and then 46.03 g (43 ml) of diisopropylethylamine and 43.08 g (58 ml) of diethyl phosphite were added
  6. customat room temperature
  7. customfor 16.5 hours
  8. washthe reaction mixture was washed with 300 ml of 3 N hydrochloric acid
  9. washfurther washed with 500 ml of a saturated saline solution
  10. dry with materialThe resulting solution was then dried over anhydrous magnesium sulfate
  11. filtrationfiltered

Sources & evidence

ORD record
ord-478fbef5b48744678bbf596dcb6ee7ec
Source dataset
uspto-grants-2014_04
Patent number
US08691996B2

Reaction notes

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