Methanol → HCID 67243842, compound

HRID 2423355Notes

Reaction equation

HRID 2423355 reaction equation
[NH2:1][C:2]1[C:9]([F:10])=[CH:8][C:5]([C:6]#[N:7])=[C:4]([F:11])[CH:3]=1.CO.[O:14](C(OC(C)(C)C)=O)[C:15]([O:17][C:18]([CH3:21])([CH3:20])[CH3:19])=O>O1CCCC1>[C:18]([O:17][C:15](=[O:14])[NH:7][CH2:6][C:5]1[CH:8]=[C:9]([F:10])[C:2]([NH2:1])=[CH:3][C:4]=1[F:11])([CH3:21])([CH3:20])[CH3:19]

Participants

5

Reactant 3

HCID 887MethanolHCID 90495Di-tert-butyl dicarbonateHCID 27359004-Amino-2,5-difluorobenzonitrile

Product 1

HCID 67243842HCID 67243842, compoundYield 51.4%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
0 °C

Procedure

A dried 50 ml two-neck round bottom flask was filled with argon gas. The solution of 4-amino-2,5-difluorobenzonitrile (0.5 g, 3.24 mmol) in tetrahydrofuran was put into the flask and cooled to 0° C. To the solution was added Borane-THF complex (2 eq, 6.49 mmol, 6.49 ml) slowly. The temperature of the mixture was raised and heated to reflux for 18 hours. After confirming the completion of the reaction with TLC, to the solution was added methanol slowly (generation of bubbles) and stirred for 2 hours. The methanol was removed under reduced pressure and the residue was extracted with ethylacetate. The ethylacetate layer was washed with water, dried over MgSO4, filtered, and concentrated under reduced pressure to yield yellow syrup. The above obtained liquid was dissolved in tetrahydrofuran and added BOC2O (1.0 eq, 0.71 g) slowly and stirred for 12 hours at room temperature. After confirming the completion of the reaction with TLC, the reaction solution was extracted with ethylacetate, washed with water and brine, dried over MgSO4, filtered and concentrated under reduced pressure. The obtained liquid was purified with column chromatography (n-hexane/ethyl acetate=4/1) to yield a white solid (0.43 g, 51.2%).

Workup

  1. additionA dried 50 ml two-neck round bottom flask was filled with argon gas
  2. additionTo the solution was added Borane-THF complex (2 eq, 6.49 mmol, 6.49 ml) slowly
  3. temperatureThe temperature of the mixture was raised
  4. temperatureheated
  5. temperatureto reflux for 18 hours
  6. customthe completion of the reaction with TLC
  7. customThe methanol was removed under reduced pressure
  8. extractionthe residue was extracted with ethylacetate
  9. washThe ethylacetate layer was washed with water
  10. dry with materialdried over MgSO4
  11. filtrationfiltered
  12. concentrationconcentrated under reduced pressure
  13. customto yield yellow syrup
  14. customThe above obtained liquid
  15. stirringstirred for 12 hours at room temperature
  16. customthe completion of the reaction with TLC
  17. extractionthe reaction solution was extracted with ethylacetate
  18. washwashed with water and brine
  19. dry with materialdried over MgSO4
  20. filtrationfiltered
  21. concentrationconcentrated under reduced pressure
  22. customThe obtained liquid was purified with column chromatography (n-hexane/ethyl acetate=4/1)

Sources & evidence

ORD record
ord-4346d0108d514f199e968c6f4b2efc42
Source dataset
uspto-grants-2011_06
Patent number
US07960584B2

Reaction notes

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