Trifluoroacetic acid → HCID 73603575, compound

HRID 1500307Notes

Reaction equation

HRID 1500307 reaction equation
[P:1]([O:19][C:20]1([C:24]2[CH:29]=[CH:28][C:27]([C:30]3[CH:35]=[CH:34][C:33]([C@H:36]4[O:40]C(C)(C)[N:38]([C:43](=[O:47])[CH:44]([F:46])[F:45])[C@@H:37]4[CH2:48][F:49])=[CH:32][CH:31]=3)=[CH:26][N:25]=2)[CH2:23][O:22][CH2:21]1)([O:11]CC1C=CC=CC=1)([O:3]CC1C=CC=CC=1)=[O:2].FC(F)(F)C(O)=O>[Pd].C(O)C.O.C(Cl)Cl>[P:1]([OH:11])([OH:3])([O:19][C:20]1([C:24]2[CH:29]=[CH:28][C:27]([C:30]3[CH:31]=[CH:32][C:33]([C@@H:36]([OH:40])[C@H:37]([NH:38][C:43](=[O:47])[CH:44]([F:46])[F:45])[CH2:48][F:49])=[CH:34][CH:35]=3)=[CH:26][N:25]=2)[CH2:21][O:22][CH2:23]1)=[O:2]

Participants

7

Reactant 2

HCID 6422Trifluoroacetic acidHCID 86713194HCID 86713194, compound

Product 1

HCID 73603575HCID 73603575, compoundYield 36.7%

Reagents, catalysts & solvents 4

HCID 23938PalladiumCatalystHCID 702EthanolSolventHCID 962WaterSolventHCID 6344DichloromethaneSolvent

Procedure

10% Palladium on carbon (45.1 mg, 0.042 mmol) is added to a degassed solution of the product of step 1, Example 24 (451.0 mg, 0.687 mmol) in ethanol (17.1 mL) and water (3.42 mL). After purging with nitrogen, 1 atm of hydrogen is bubbled through the reaction mixture for 5 min before being left under 1 atm of hydrogen. After 1 hour the reaction mixture is filtered through solka floc, and the cake washed with ethanol. The filtrate is concentrated and azeotroped with ethanol to afford a white foam. The crude intermediate is taken up in methylene chloride (4.51 mL) and cooled at 0° C. before trifluoroacetic acid (1.06 mL, 13.7 mmol) is added and the mixture warmed to room temperature. After 4 hours the mixture is concentrated and azeotroped with methylene chloride then purified by reverse phase CombiFlash (30 g column) eluting with 0-25% acetonitrile in water (with 0.1% trifluoroacetic acid) to afford the title compound (120 mg): 1H NMR (300 MHz, DMSO-6) δ 4.27-4.52 (m, 2.5H), 4.66-4.69 (m, 0.5H), 4.87-4.90 (m, 1H), 4.97 (d, 2H), 5.08 (d, 2H), 6.20 (t, 1H), 7.48 (d, 2H), 7.69 (d, 1H), 7.75 (d, 2H), 8.14-8.17 (dd, 1H), 8.83 (d, 1H), 8.96-8.97 (m, 1H). MS (ESI+) m/z 477.1 [M+H].

Workup

  1. customAfter purging with nitrogen, 1 atm of hydrogen
  2. customis bubbled through the reaction mixture for 5 min
  3. waitbefore being left under 1 atm of hydrogen
  4. filtrationAfter 1 hour the reaction mixture is filtered through solka floc
  5. washthe cake washed with ethanol
  6. concentrationThe filtrate is concentrated
  7. customazeotroped with ethanol
  8. customto afford a white foam
  9. additionis added
  10. concentrationAfter 4 hours the mixture is concentrated
  11. customazeotroped with methylene chloride
  12. customthen purified by reverse phase CombiFlash (30 g column)
  13. washeluting with 0-25% acetonitrile in water (with 0.1% trifluoroacetic acid)

Sources & evidence

ORD record
ord-5b65a56f1aff44e3bca47b5ae3d99bac
Source dataset
uspto-grants-2015_12
Patent number
US09206126B2

Reaction notes

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