tert-Butanol → N-ethoxycarbonyl-4-t-butyl-2-fluoroaniline

HRID 2116814Notes

Reaction equation

HRID 2116814 reaction equation
[F:1][C:2]1[CH:13]=[CH:12][CH:11]=[CH:10][C:3]=1[NH:4][C:5]([O:7][CH2:8][CH3:9])=[O:6].[C:14](O)([CH3:17])([CH3:16])[CH3:15].CCCCCC>S(=O)(=O)(O)O>[CH2:8]([O:7][C:5]([NH:4][C:3]1[CH:10]=[CH:11][C:12]([C:14]([CH3:17])([CH3:16])[CH3:15])=[CH:13][C:2]=1[F:1])=[O:6])[CH3:9]

Participants

5

Reactant 3

HCID 6386tert-Butanol3×HCID 8058HexaneHCID 242730ethyl N-(2-fluorophenyl)carbamate

Product 1

HCID 10243326N-ethoxycarbonyl-4-t-butyl-2-fluoroanilineYield 111%

Reagents, catalysts & solvents 1

HCID 1118Sulfuric AcidSolvent

Conditions

Temperature
70 °C

Procedure

2-Fluoro-N-ethoxycarbonylaniline (1.00 g, 5.46 mmol) prepared as described in Example 1 was dissolved in 77.6% sulfuric acid (5.00 g) to prepare a solution. t-Butyl alcohol (0.440 g, 6.01 mmol) was added dropwise to the solution under a nitrogen atmosphere over a period of 30 min while stirring and heating the solution at 70° C. After the completion of the dropwise addition, the reaction solution was vigorously stirred at the same temperature for one hr. Thereafter, t-butyl alcohol (0.440 g, 6.01 mmol) was again added dropwise thereto over a period of 30 min. After the completion of the dropwise addition, the reaction solution was vigorously stirred at the same temperature for one hr. t-Butyl alcohol (0.440 g, 6.01 mmol) was again added dropwise thereto over a period of 30 min. After the completion of the dropwise addition, the reaction solution was vigorously stirred at the same temperature for one hr. The reaction solution was cooled to room temperature. n-Hexane (10 mL) was then added to the cooled reaction solution to carry out extraction for separation of the mixture into a sulfuric acid layer and an organic layer. n-Hexane (10 mL) was again added to the sulfuric acid layer to carry out extraction for separation of an organic layer. The organic layers were combined, and the combined organic layer was washed with water and saturated brine in that order. The solvent was then removed from the organic layer by distillation to give 1.45 g of N-ethoxycarbonyl-4-t-butyl-2-fluoroaniline as an oily crude product (yield on weight basis 111%). The crude product was further subjected to separation and purification by column chromatography on silica gel to give 1.17 g of a mixture of 4-t-butyl-2-fluoro-N-ethoxycarbonylaniline with 5-t-butyl-2-fluoro-N-ethoxycarbonylaniline (yield 90%, 4-t-Bu: 5-t-Bu=82:18).

Workup

  1. customto prepare a solution
  2. additionAfter the completion of the dropwise addition
  3. stirringthe reaction solution was vigorously stirred at the same temperature for one hr
  4. additionAfter the completion of the dropwise addition
  5. stirringthe reaction solution was vigorously stirred at the same temperature for one hr
  6. waitover a period of 30 min
  7. additionAfter the completion of the dropwise addition
  8. stirringthe reaction solution was vigorously stirred at the same temperature for one hr
  9. temperatureThe reaction solution was cooled to room temperature
  10. extractionextraction
  11. customfor separation of the mixture into a sulfuric acid layer
  12. additionn-Hexane (10 mL) was again added to the sulfuric acid layer
  13. extractionextraction
  14. customfor separation of an organic layer
  15. washthe combined organic layer was washed with water and saturated brine in that order
  16. customThe solvent was then removed from the organic layer by distillation

Sources & evidence

ORD record
ord-c7241156892a4745b80b49284339da88
Source dataset
uspto-grants-2008_10
Patent number
US07439382B2

Reaction notes

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