Ethyl Acetate → HCID 69516031, compound

HRID 458433Notes

Reaction equation

HRID 458433 reaction equation
C(O[C:6]([N:8]1[CH2:12][CH2:11][CH2:10][C@H:9]1[C:13]1[NH:14][C:15]([CH2:35][C:36]2[CH:41]=[CH:40][C:39]([F:42])=[CH:38][C:37]=2[F:43])=[CH:16][CH:17]([C:24]2[N:25]=[CH:26][C:27]([C:30]([O:32][CH2:33][CH3:34])=[O:31])=[N:28][CH:29]=2)[C:18]=1C(OCC)=O)=[O:7])(C)(C)C.CCOC(C)=O>CC#N.O>[F:43][C:37]1[CH:38]=[C:39]([F:42])[CH:40]=[CH:41][C:36]=1[CH2:35][C:15]1[CH:16]=[C:17]([C:24]2[N:25]=[CH:26][C:27]([C:30]([O:32][CH2:33][CH3:34])=[O:31])=[N:28][CH:29]=2)[C:18]2[C:6](=[O:7])[N:8]3[C@@H:9]([CH2:10][CH2:11][CH2:12]3)[C:13]=2[N:14]=1

Participants

5

Reactant 2

HCID 8857Ethyl AcetateHCID 69515680HCID 69515680, compound

Product 1

HCID 69516031HCID 69516031, compoundYield 26%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6342AcetonitrileSolvent

Procedure

Ethyl 5-[2-[(2S)-1-(tert-butoxycarbonyl)pyrrolidinyl]-6-(2,4-difluorobenzyl)-3-(ethoxycarbonyl)-1,4-dihydro-4-pyridinyl]-2-pyrazinecarboxylate (1.3 g, 2.17 mmol) was dissolved in 8 mL of CH3CN and 4 mL of H2O. Ceric ammonium nitrate (2.38 g, 4.34 mmol) was added and the reaction mixture stirred at ambient temperature for 30 min and then EtOAc was added and the organics extracted and washed with H2O, brine, and then dried (Na2SO4), filtered and concentrated to a brown solid. The solid was subjected to TFA (4.5 mL in 1 mL CH2Cl2) for 1 h and then concentrated. The residue was redissolved in CH2Cl2 (5 mL) and treated with Et3N (3 mL). After 16 h the reaction mixture was concentrated to a brown foam. The residue was redissolved in EtOAc and washed 1× pH 4.5 buffer, 1× brine and the organics dried (Na2SO4), filtered and concentrated to yield 0.250 g (26% yield) of the title compound as a tan solid. 1H NMR (CDCl3, 400 MHz) δ 9.41 (s, 1H), 9.34 (s, 1H), 7.58 (s, 1H), 7.26–7.21 (m, 1H), 6.80 (dd, J=16.4, 7.4 Hz, 2H), 4.75 (dd, J=10.3, 6.2 Hz, 1H), 4.51 (dd,J=14.2, 7.1 Hz, 2H), 4.27 (s, 2H), 3.78–3.68 (m, 1H), 3.45–3.39 (m, 1H), 2.54–2.43 (m, 1H), 2.37–2.32 (m, 2H), 1.46–1.38 (m, 1H), 1.23 (t, J=7.2 Hz, 3H); ESMS m/z 451 (M+H)+, 449 (M−H)+.

Workup

  1. extractionthe organics extracted
  2. washwashed with H2O, brine
  3. dry with materialdried (Na2SO4)
  4. filtrationfiltered
  5. concentrationconcentrated to a brown solid
  6. waitThe solid was subjected to TFA (4.5 mL in 1 mL CH2Cl2) for 1 h
  7. concentrationconcentrated
  8. dissolutionThe residue was redissolved in CH2Cl2 (5 mL)
  9. additiontreated with Et3N (3 mL)
  10. concentrationAfter 16 h the reaction mixture was concentrated to a brown foam
  11. dissolutionThe residue was redissolved in EtOAc
  12. washwashed 1× pH 4.5 buffer
  13. dry with material1× brine and the organics dried (Na2SO4)
  14. filtrationfiltered
  15. concentrationconcentrated

Sources & evidence

ORD record
ord-975daad38e1d4b6eb697c0d1e38841b2
Source dataset
uspto-grants-2007_03
Patent number
US07189851B2

Reaction notes

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