Trifluoroacetic acid → HCID 90411400, compound

HRID 1521954Notes

Reaction equation

HRID 1521954 reaction equation
[F:1][C:2]1[CH:3]=[CH:4][C:5]([O:39][CH3:40])=[C:6]([C:8]2[CH:13]=[CH:12][N:11]=[C:10]3[N:14](S(C4C=CC=CC=4)(=O)=O)[C:15]([C:17]4[CH2:22][CH2:21][N:20](C(OC(C)(C)C)=O)[CH2:19][CH:18]=4)=[CH:16][C:9]=23)[CH:7]=1.[OH-].[Na+].FC(F)(F)C(O)=O>O1CCOCC1.ClCCl>[F:1][C:2]1[CH:3]=[CH:4][C:5]([O:39][CH3:40])=[C:6]([C:8]2[CH:13]=[CH:12][N:11]=[C:10]3[NH:14][C:15]([C:17]4[CH2:22][CH2:21][NH:20][CH2:19][CH:18]=4)=[CH:16][C:9]=23)[CH:7]=1

Participants

6

Reactant 3

HCID 6422Trifluoroacetic acidHCID 14798Sodium HydroxideHCID 90411407HCID 90411407, compound

Product 1

HCID 90411400HCID 90411400, compound

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 312751,4-DioxaneSolvent

Procedure

A mixture of Example 87C (400.0 mg, 0.710 mmol) and 20% sodium hydroxide (0.7 mL) solution in dioxane (6 mL) was heated at 90° C. for 6 hours. The mixture was concentrated and the residue was treated with ethyl acetate and washed with water. The organic layer was dried over magnesium sulfate, filtered and concentrated until most of solvent was evaporated. The solids were filtered, washed with ethyl acetate/heptane, and dried under vacuum to afford the protected intermediate. The intermediate was dissolved in dichloromethane (8 mL) and treated with trifluoroacetic acid (0.547 mL, 7.10 mmol) and the mixture was stirred for 3 hours and concentrated. The residue was dissolved in 2.5 mL methanol and treated with 4 mL 1M hydrogen chloride in ether. After stirring for 15 minutes, the mixture was treated with ether. The solids were filtered, washed with ether, and dried under vacuum to afford the title compound as a hydrochloride salt. 1H NMR (400 MHz, CD3OD) δ 2.93-2.83 (m, 2H), 3.50 (t, J=6.1 Hz, 2H), 3.83 (s, 3H), 4.01-3.96 (m, 2H), 6.65-6.59 (m, 1H), 6.74 (s, 1H), 7.38-7.21 (m, 3H), 7.58 (d, J=6.1 Hz, 1H), 8.36 (d, J=6.1 Hz, 1H). MS (ESI+) m/z 324.1 (M+H)+.

Workup

  1. concentrationThe mixture was concentrated
  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 until most of solvent
  7. customwas evaporated
  8. filtrationThe solids were filtered
  9. washwashed with ethyl acetate/heptane
  10. customdried under vacuum
  11. customto afford the protected intermediate
  12. concentrationconcentrated
  13. dissolutionThe residue was dissolved in 2.5 mL methanol
  14. additiontreated with 4 mL 1M hydrogen chloride in ether
  15. stirringAfter stirring for 15 minutes
  16. additionthe mixture was treated with ether
  17. filtrationThe solids were filtered
  18. washwashed with ether
  19. customdried under vacuum

Sources & evidence

ORD record
ord-32c0f599b1ee4e4dbdca417c2dc822cb
Source dataset
uspto-grants-2015_07
Patent number
US09073922B2

Reaction notes

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