Trifluoroacetic acid → HCID 68965162, compound

HRID 2376147Notes

Reaction equation

HRID 2376147 reaction equation
C(OC([N:8]([C@@H:20]1[CH2:24][CH2:23][N:22]([C:25]([CH:27]2[CH2:32][CH2:31][CH2:30][CH2:29][CH2:28]2)=[O:26])[CH2:21]1)[C:9]1[N:14]=[C:13](C=CC([O-])=O)[CH:12]=[CH:11][CH:10]=1)=O)(C)(C)C.[C:33]1([O:39]C)[CH:38]=[CH:37]C=CC=1.FC(F)(F)C(O)=[O:44].C([O-])(O)=O.[Na+]>ClCCl.O1CCCC1.CO.[OH-].[Na+].CCOC(C)=O.O>[CH:27]1([C:25]([N:22]2[CH2:23][CH2:24][C@@H:20]([NH:8][C:9]3[N:14]=[CH:13][C:12](/[CH:37]=[CH:38]/[C:33]([OH:39])=[O:44])=[CH:11][CH:10]=3)[CH2:21]2)=[O:26])[CH2:28][CH2:29][CH2:30][CH2:31][CH2:32]1

Participants

11

Reactant 4

HCID 6422Trifluoroacetic acidHCID 7519AnisoleHCID 516892Sodium BicarbonateHCID 86760789HCID 86760789, compound

Product 1

HCID 68965162HCID 68965162, compoundYield 97%

Reagents, catalysts & solvents 6

HCID 887MethanolSolventHCID 962WaterSolventHCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolventHCID 14798Sodium HydroxideSolvent

Conditions

Temperature
25 °C

Procedure

To an ice-cooled solution of ethyl (2E)-3-(6-{(tert-butoxycarbonyl)[(3R)-1-(cyclohexylcarbonyl)-3-pyrrolidinyl]amino}-3-{pyridinyl}acrylate (355 mg) in dichloromethane (2 ml) was added anisole (1.0 ml) and trifluoroacetic acid (2.0 ml), the mixture was stirred at 25° C. for 1 hour. The mixed solution was poured into a mixture of water and AcOEt. The pH of the aqueous layer was adjusted to ca.9 with NaHCO3. The organic layer was separated, washed with brine, dried over sodium sulfate and evaporated under reduced pressure to give syrup. The residue was dissolved in a mixed solvent of tetrahydrofuran (6 ml) and methanol (2.5 ml), and 1 mol/L-NaOH (1.5 mL) was added to the solution at 25° C. The mixture was stirred at 50° C. for 1.5 hours. The reaction mixture was evaporated in vacuo, the resulting residue was poured into a mixture of water and AcOEt. The pH of the aqueous layer was adjusted to ca.5 with 1 mol/L hydrochloric acid. The organic layer was separated, dried over sodium sulfate and evaporated under reduced pressure to give (2E)-3-(6-{[(3R)-1-(cyclohexylcarbonyl)-3-pyrrolidinyl]amino}-3-pyridinyl)acrylic acid (250 mg, 97%) as powder.

Workup

  1. customThe organic layer was separated
  2. washwashed with brine
  3. dry with materialdried over sodium sulfate
  4. customevaporated under reduced pressure
  5. customto give syrup
  6. additionwas added to the solution at 25° C
  7. stirringThe mixture was stirred at 50° C. for 1.5 hours
  8. customThe reaction mixture was evaporated in vacuo
  9. additionthe resulting residue was poured into a mixture of water and AcOEt
  10. customThe organic layer was separated
  11. dry with materialdried over sodium sulfate
  12. customevaporated under reduced pressure

Sources & evidence

ORD record
ord-0287560c986e4dda9647b1cd63e1a1db
Source dataset
uspto-grants-2008_12
Patent number
US07465731B2

Reaction notes

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