Bromine → HCID 66959145, compound

HRID 2283848Notes

Reaction equation

HRID 2283848 reaction equation
[Br:1]Br.[C:3]([C:5]1[CH:9]=[C:8]([CH2:10][C:11]([NH:14][C:15](=[O:21])[O:16][C:17]([CH3:20])([CH3:19])[CH3:18])([CH3:13])[CH3:12])[N:7]([CH2:22][CH2:23][O:24][CH3:25])[N:6]=1)#[N:4].C([O-])(=O)C.[K+].S(=O)(=O)(O)[O-].[Na+]>C(O)(=O)C>[Br:1][C:9]1[C:5]([C:3]#[N:4])=[N:6][N:7]([CH2:22][CH2:23][O:24][CH3:25])[C:8]=1[CH2:10][C:11]([NH:14][C:15](=[O:21])[O:16][C:17]([CH3:18])([CH3:19])[CH3:20])([CH3:13])[CH3:12]

Participants

6

Reactant 4

HCID 24408BromineHCID 516919Sodium BisulfateHCID 517044Potassium AcetateHCID 66958323HCID 66958323, compound

Product 1

HCID 66959145HCID 66959145, compoundYield 91.8%

Reagents, catalysts & solvents 1

HCID 176Acetic AcidSolvent

Procedure

Bromine (19.5 g, 122 mmol) was added in a single portion to a solution of tert-butyl 2-[3-cyano-1-(2-methoxyethyl)-1H-pyrazol-5-yl]-1,1-dimethylethylcarbamate (28.07 g, 87.1 mmol) and potassium acetate (12.8 g, 131 mmol) in acetic acid (174.2 mL). After 16 hours saturated aqueous sodium bisulfate was added until the reaction mixture was colorless. The acetic acid was removed under reduced pressure at about 30° C. The residue was made basic with 2 M sodium carbonate and then extracted with tert-butyl methyl ether (×3). The extracts were combined, dried over magnesium sulfate, and concentrated under reduced pressure. Analysis by HPLC indicated that the BOC group had been partially removed. The material was dissolved in dichloromethane (50 mL), combined with di-tert-butyl dicarbonate, and stirred for 9 hours. The reaction mixture was concentrated under reduced pressure and the residue was purified by IFC (65+M cartridge eluting with a gradient of 40 to 50% tert-butyl methyl ether in hexanes) to provide 32.1 g of tert-butyl 2-[4-bromo-3-cyano-1-(2-methoxyethyl)-1H-pyrazol-5-yl]-1,1-dimethylethylcarbamate as a colorless, viscous resin.

Workup

  1. customThe acetic acid was removed under reduced pressure at about 30° C
  2. extractionextracted with tert-butyl methyl ether (×3)
  3. dry with materialdried over magnesium sulfate
  4. concentrationconcentrated under reduced pressure
  5. customhad been partially removed
  6. dissolutionThe material was dissolved in dichloromethane (50 mL)
  7. concentrationThe reaction mixture was concentrated under reduced pressure
  8. customthe residue was purified by IFC (65+M cartridge
  9. washeluting with a gradient of 40 to 50% tert-butyl methyl ether in hexanes)

Sources & evidence

ORD record
ord-1aab518130ff4a6a8c977e6e01d55db9
Source dataset
uspto-grants-2015_09
Patent number
US09145410B2

Reaction notes

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