Trifluoroacetic acid → HCID 90412326, compound

HRID 1521999Notes

Reaction equation

HRID 1521999 reaction equation
[F:1][C:2]1[C:3]([C:33]2[CH:38]=[C:37]([F:39])[CH:36]=[CH:35][C:34]=2[O:40][CH3:41])=[C:4]2[CH:10]=[C:9]([C:11]3[CH2:16][CH2:15][N:14](C(OC(C)(C)C)=O)[CH2:13][CH:12]=3)[N:8](S(C3C=CC=CC=3)(=O)=O)[C:5]2=[N:6][CH:7]=1.[OH-].[Na+].FC(F)(F)C(O)=O>O1CCOCC1.ClCCl>[F:1][C:2]1[C:3]([C:33]2[CH:38]=[C:37]([F:39])[CH:36]=[CH:35][C:34]=2[O:40][CH3:41])=[C:4]2[CH:10]=[C:9]([C:11]3[CH2:16][CH2:15][NH:14][CH2:13][CH:12]=3)[NH:8][C:5]2=[N:6][CH:7]=1

Participants

6

Reactant 3

HCID 6422Trifluoroacetic acidHCID 14798Sodium HydroxideHCID 90412281HCID 90412281, compound

Product 1

HCID 90412326HCID 90412326, compound

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 312751,4-DioxaneSolvent

Procedure

A mixture of Example 231D (2.00 g, 3.44 mmol) and 5M sodium hydroxide (2.407 mL, 12.04 mmol) in dioxane (20 mL) was heated at 90° C. for 8 hours. After concentration, the residue was treated with ethyl acetate and washed with water. The organic layer was dried over magnesium sulfate, filtered, concentrated, and purified on silica gel using an ISCO Companion eluting with heptanes/ethyl acetate (6:4 to 4:6) to give the protected intermediate. A solution of the intermediate in dichloromethane (25 mL) was treated with trifluoroacetic acid (2.27 mL, 29.4 mmol) and the mixture was stirred for 3 hours and concentrated. The residue was dissolved in 6 mL methanol and treated slowly with 5 mL 2M hydrogen chloride in ether. The suspension was sonicated, diluted with ether and stirred for 10 minutes. The solid was filtered, washed with ether and vacuum oven-dried to give the title compound as a hydrochloride salt. MS (ESI+) m/z 342.1 (M+H)+.

Workup

  1. concentrationAfter concentration
  2. additionthe residue was treated with ethyl acetate
  3. washwashed with water
  4. dry with materialThe organic layer was dried over magnesium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated
  7. custompurified on silica gel using an ISCO Companion
  8. washeluting with heptanes/ethyl acetate (6:4 to 4:6)
  9. customto give the protected intermediate
  10. concentrationconcentrated
  11. dissolutionThe residue was dissolved in 6 mL methanol
  12. additiontreated slowly with 5 mL 2M hydrogen chloride in ether
  13. customThe suspension was sonicated
  14. additiondiluted with ether
  15. stirringstirred for 10 minutes
  16. filtrationThe solid was filtered
  17. washwashed with ether and vacuum
  18. customoven-dried

Sources & evidence

ORD record
ord-52fdc51175bd4df2bfbe7a8ec4356e85
Source dataset
uspto-grants-2015_07
Patent number
US09073922B2

Reaction notes

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