Sodium Hydroxide → phenyl (3-(tert-butyl)-1-(p-tolyl)-1H-pyrazol-5-yl)carbamate

HRID 1666770Notes

Reaction equation

HRID 1666770 reaction equation
[C:1]([C:5]1[CH:9]=[C:8]([NH2:10])[N:7]([C:11]2[CH:16]=[CH:15][C:14]([CH3:17])=[CH:13][CH:12]=2)[N:6]=1)([CH3:4])([CH3:3])[CH3:2].[OH-].[Na+].Cl[C:21]([O:23][C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1)=[O:22]>CCOC(C)=O>[C:1]([C:5]1[CH:9]=[C:8]([NH:10][C:21](=[O:22])[O:23][C:24]2[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=2)[N:7]([C:11]2[CH:12]=[CH:13][C:14]([CH3:17])=[CH:15][CH:16]=2)[N:6]=1)([CH3:4])([CH3:3])[CH3:2]

Participants

5

Reactant 3

HCID 14798Sodium HydroxideHCID 15891Phenyl chloroformateHCID 29741323-tert-butyl-1-(4-methylphenyl)-1H-pyrazol-5-amine

Product 1

HCID 11057211phenyl (3-(tert-butyl)-1-(p-tolyl)-1H-pyrazol-5-yl)carbamateYield 286.9%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
60 °C

Procedure

To a solution of 3-tert-butyl-1-p-tolyl-1H-pyrazol-5-amine (102.9 g, 448.9 mmol) in EtOAc (1 L) at 10.9° C. was added a NaOH solution (2.5 M, 269 mL), and the biphasic reaction mixture warmed to 15.9 and then stabilized. Phenyl chloroformate (98.4 g, 156.5 mmol) was added in one portion and the temperature rose to 25.5 and then stabilized. The ice bath was removed and the reaction was monitored by HPLC. After 1 hour an additional 25 mL of 2.5 M NaOH was added. The reaction mixture was stirred overnight, and then diluted with EtOAc (200 mL). The organic layer was washed with brine (1 L), dried over Na2SO4 (200 g) and concentrated to about 400 to 500 mL of EtOAc. The concentrated solution was warmed to 60° C. After the solids had dissolved, heptane (2 L) was slowly added, during which solids formed. After stirring for 30 minutes the solid was collected via filtration and the cake was washed with 400-500 mL of heptane. The cake was dried in a vacuum oven at ambient temperature to yield 156.9 g (95.0%) of the title compound. 1H NMR (400 MHz, CDCl3) δ 7.39-7.31 (m, 6H), 7.26-7.225 (m, 2H), 7.13 (br s, 2H), 6.96 (br s, 1H), 6.47 (br s, 1H), 2.42 (s, 3H), 1.34 (s, 9H).

Workup

  1. customthe biphasic reaction mixture
  2. temperaturewarmed to 15.9
  3. customThe ice bath was removed
  4. additionAfter 1 hour an additional 25 mL of 2.5 M NaOH was added
  5. additiondiluted with EtOAc (200 mL)
  6. washThe organic layer was washed with brine (1 L)
  7. dry with materialdried over Na2SO4 (200 g)
  8. concentrationconcentrated to about 400 to 500 mL of EtOAc
  9. dissolutionAfter the solids had dissolved
  10. additionheptane (2 L) was slowly added, during which solids
  11. customformed
  12. stirringAfter stirring for 30 minutes the solid
  13. filtrationwas collected via filtration
  14. washthe cake was washed with 400-500 mL of heptane
  15. customThe cake was dried in a vacuum oven at ambient temperature

Sources & evidence

ORD record
ord-3da95f4b634341d99f1829631d0b3a14
Source dataset
uspto-grants-2011_10
Patent number
US08044083B2

Reaction notes

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