Potassium Carbonate → HCID 53482820, compound

HRID 1037495Notes

Reaction equation

HRID 1037495 reaction equation
C([O:4][C@@H:5]([CH3:52])[C:6]([N:8]([CH2:35][C@H:36]1[C@@H:40]([F:41])[CH2:39][N:38](C(OCC2C=CC=CC=2)=O)[CH2:37]1)[C@@H:9]([C:14]1[N:18]([CH2:19][C:20]2[CH:25]=[CH:24][CH:23]=[C:22]([F:26])[CH:21]=2)[N:17]=[C:16]([C:27]2[CH:32]=[C:31]([F:33])[CH:30]=[CH:29][C:28]=2[F:34])[N:15]=1)[C:10]([CH3:13])([CH3:12])[CH3:11])=[O:7])(=O)C.C(=O)([O-])[O-].[K+].[K+]>CCOC(C)=O.CO.[Pd]>[F:34][C:28]1[CH:29]=[CH:30][C:31]([F:33])=[CH:32][C:27]=1[C:16]1[N:15]=[C:14]([C@H:9]([N:8]([CH2:35][C@H:36]2[C@@H:40]([F:41])[CH2:39][NH:38][CH2:37]2)[C:6](=[O:7])[C@@H:5]([OH:4])[CH3:52])[C:10]([CH3:11])([CH3:12])[CH3:13])[N:18]([CH2:19][C:20]2[CH:25]=[CH:24][CH:23]=[C:22]([F:26])[CH:21]=2)[N:17]=1

Participants

6

Reactant 2

HCID 11430Potassium CarbonateHCID 131730886HCID 131730886, compound

Product 1

HCID 53482820HCID 53482820, compoundYield 57%

Reagents, catalysts & solvents 3

HCID 23938PalladiumCatalystHCID 887MethanolSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of (3R,4R)-benzyl 3-(((S)-2-acetoxy-N-((R)-1-(3-(2,5-difluorophenyl)-1-(3-fluorobenzyl)-1H-1,2,4-triazol-5-yl)-2,2-dimethylpropyl)propanamido)methyl)-4-fluoropyrrolidine-1-carboxylate (2.24 g, 3.09 mmol) in degassed EtOAc (25 mL, 0.1 M solution) was added Pd/C (224 mg, 10 wt %) under anhydrous N2 atmosphere. After flushed with hydrogen gas, the reaction mixture equipped with a hydrogen gas balloon was stirred at room temperature for overnight. The reaction mixture was filtered through Celite® pad that was washed with EtOAc. The volatile organic filtrate was removed in vacuo to give the crude amine. Then, the crude product was dissolved in MeOH (200 mL, 0.015 M solution) followed by addition of anhydrous potassium carbonate (4.2 g, 30.9 mmol). The reaction was then stirred for 15 min at room temperature. After white precipitate was removed by filtration, the organic filtrate was concentrated in vacuo. The crude product was purified by preparative reverse phase HPLC. The combined fractions of the product were neutralized with saturated NaHCO3 solution, which was then extracted with EtOAc (200 mL). The organic layer was dried over anhydrous sodium sulfate, filtered and concentrated in vacuo. The dried product was then dissolved in acetonitrile and water (1:1 ratio) and lyophilized for 48 h. The white powdery (S)—N—((R)-1-(3-(2,5-difluorophenyl)-1-(3-fluorobenzyl)-1H-1,2,4-triazol-5-yl)-2,2-dimethylpropyl)-N-(((3S,4R)-4-fluoropyrrolidin-3-yl)methyl)-2-hydroxypropanamide was obtained in 57% yield (962 mg, over 3 steps) as a free amine 1H NMR (CD3OD, 400 MHz): 7.81 (1H, m), 7.40-7.16 (5H, m), 7.06 (1H, m), 6.12 (1H, s), 5.44 (2H, m), 4.77 (2H, m), 3.87 (1H, m), 2.82 (2H, m), 2.28 (1H, m), 2.17 (1H, m), 1.95 (1H, m), 1.43 (3H, m), 1.22 (1H, m), 0.91 (9H, s). LC/MS (uplc): MH+ 548.3, 0.94 min.

Workup

  1. customAfter flushed with hydrogen gas
  2. customthe reaction mixture equipped with a hydrogen gas balloon
  3. filtrationThe reaction mixture was filtered through Celite® pad that
  4. washwas washed with EtOAc
  5. customThe volatile organic filtrate was removed in vacuo
  6. customto give the crude amine
  7. stirringThe reaction was then stirred for 15 min at room temperature
  8. customAfter white precipitate was removed by filtration
  9. concentrationthe organic filtrate was concentrated in vacuo
  10. customThe crude product was purified by preparative reverse phase HPLC
  11. extractionwas then extracted with EtOAc (200 mL)
  12. dry with materialThe organic layer was dried over anhydrous sodium sulfate
  13. filtrationfiltered
  14. concentrationconcentrated in vacuo
  15. dissolutionThe dried product was then dissolved in acetonitrile
  16. waitwater (1:1 ratio) and lyophilized for 48 h

Sources & evidence

ORD record
ord-19b7eae395614f4eb3ac04c5c9a66f36
Source dataset
uspto-grants-2013_10
Patent number
US08546434B2

Reaction notes

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