Trifluoromethanesulfonic anhydride → HCID 18536113, compound

HRID 412175Notes

Reaction equation

HRID 412175 reaction equation
[C:1]([C:3]1[CH:10]=[CH:9][C:6]([CH2:7]O)=[CH:5][C:4]=1[F:11])#[N:2].C(N(C(C)C)CC)(C)C.S(OS(C(F)(F)F)(=O)=O)(C(F)(F)F)(=O)=O.[CH3:36][S:37]([O:40][C:41]1[CH:50]=[C:49]2[C:44]([CH:45]=[CH:46][CH:47]=[C:48]2[N:51]2[CH2:56][CH2:55][N:54]([CH2:57][CH2:58][C:59]3[N:60]=[CH:61][N:62](C(C4C=CC=CC=4)(C4C=CC=CC=4)C4C=CC=CC=4)[CH:63]=3)[CH2:53][C:52]2=[O:83])=[CH:43][CH:42]=1)(=[O:39])=[O:38]>ClCCl>[CH3:36][S:37]([O:40][C:41]1[CH:50]=[C:49]2[C:44]([CH:45]=[CH:46][CH:47]=[C:48]2[N:51]2[CH2:56][CH2:55][N:54]([CH2:57][CH2:58][C:59]3[N:60]([CH2:7][C:6]4[CH:9]=[CH:10][C:3]([C:1]#[N:2])=[C:4]([F:11])[CH:5]=4)[CH:61]=[N:62][CH:63]=3)[CH2:53][C:52]2=[O:83])=[CH:43][CH:42]=1)(=[O:39])=[O:38]

Participants

6

Reactant 4

HCID 67749Trifluoromethanesulfonic anhydrideHCID 81531DiisopropylethylamineHCID 118296312-Fluoro-4-(hydroxymethyl)benzonitrileHCID 18536158HCID 18536158, compound

Product 1

HCID 18536113HCID 18536113, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Conditions

Temperature
-78 °C

Procedure

To a solution of the product from Step J (15 mg, 0.75 mmol) in 3 mL of dichloromethane at −78° C. was diisopropylethylamine (0.40 mL, 2.28 mmol), followed by triflic anhydride (0.128 mL, 0.76 mmol). After 20 minutes, a solution of the product from Step G (500 mg, 0.762 mmol) in 2 mL of dichloromethane was added, and the reaction was stirred at −78° C. for 30 minutes, and at room temperature for 1.5 hours. After concentrating the reaction in vacuo, 5 mL of methanol was added and the solution was heated at reflux for 30 minutes. The solution was concentrated in vacuo, acidified with 5% HCl solution, triturated with hexane, and partitioned between EtOAc and 20% NaOH solution. The organic layer was washed with brine, dried (MgSO4), filtered, and concentrated in vacuo to provide the titled product.

Workup

  1. customat −78° C.
  2. waitat room temperature for 1.5 hours
  3. concentrationAfter concentrating
  4. customthe reaction in vacuo, 5 mL of methanol
  5. additionwas added
  6. temperaturethe solution was heated
  7. temperatureat reflux for 30 minutes
  8. concentrationThe solution was concentrated in vacuo
  9. customtriturated with hexane
  10. custompartitioned between EtOAc and 20% NaOH solution
  11. washThe organic layer was washed with brine
  12. dry with materialdried (MgSO4)
  13. filtrationfiltered
  14. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-aa00799ba2b44a1b94195ef01f309e8c
Source dataset
uspto-grants-2003_05
Patent number
US06562823B1

Reaction notes

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