Hydrogen Peroxide → HCID 90203915, compound

HRID 1480312Notes

Reaction equation

HRID 1480312 reaction equation
[C:1]([CH:3]([C:23]1([CH3:27])[CH2:26][O:25][CH2:24]1)[NH:4][C:5]([C:7]1[CH:12]=[C:11]([O:13][C@@H:14]([CH3:19])[C:15]([F:18])([F:17])[F:16])[C:10]([CH:20]2[CH2:22][CH2:21]2)=[CH:9][N:8]=1)=[O:6])#[N:2].[OH-:28].[Na+].OO>C(O)C>[NH2:2][C:1](=[O:28])[CH:3]([NH:4][C:5]([C:7]1[CH:12]=[C:11]([O:13][C@@H:14]([CH3:19])[C:15]([F:16])([F:18])[F:17])[C:10]([CH:20]2[CH2:21][CH2:22]2)=[CH:9][N:8]=1)=[O:6])[C:23]1([CH3:27])[CH2:26][O:25][CH2:24]1

Participants

5

Reactant 3

HCID 784Hydrogen PeroxideHCID 14798Sodium HydroxideHCID 90214939HCID 90214939, compound

Product 1

HCID 90203915HCID 90203915, compound

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

To a solution of N-[cyano-(3-methyloxetan-3-yl)methyl]-5-cyclopropyl-4-[(1S)-2,2,2-trifluoro-1-methyl-ethoxy]pyridine-2-carboxamide (example 251c, 0.17 g, 443 μmol) in ethanol (3 ml) was added a 4M aqueous solution of sodium hydroxide (554 μl, 2.22 mmol) and H2O2 35% aqueous solution (215 mg, 190 μl, 2.22 mmol). The reaction mixture was stirred at room temperature overnight. The reaction was then concentrated in vacuo and diluted with ethyl acetate. The organic phase was extracted with a 1M aqueous solution of sodium bicarbonate. The organic phase was collected and the aqueous phase was back-extracted with ethyl acetate. The combined organic phases were dried over sodium sulfate and evaporated down to dryness. The crude material was purified by flash chromatography on silica eluting with a heptane-ethyl acetate gradient to yield the mixture of epimers which was then separated into its individual epimers by preparative chiral HPLC (Chiralpak AD, ethanol/heptane) and the title compound was the second epimer collected and isolated as colorless oil; MS (ESI, m/z): 402.6 (M+H+).

Workup

  1. concentrationThe reaction was then concentrated in vacuo
  2. additiondiluted with ethyl acetate
  3. extractionThe organic phase was extracted with a 1M aqueous solution of sodium bicarbonate
  4. customThe organic phase was collected
  5. extractionthe aqueous phase was back-extracted with ethyl acetate
  6. dry with materialThe combined organic phases were dried over sodium sulfate
  7. customevaporated down to dryness
  8. customThe crude material was purified by flash chromatography on silica eluting with a heptane-ethyl acetate gradient
  9. customto yield
  10. additionthe mixture of epimers which
  11. customwas then separated into its individual epimers by preparative chiral HPLC (Chiralpak AD, ethanol/heptane)
  12. customcollected
  13. customisolated as colorless oil

Sources & evidence

ORD record
ord-8009fe9a40d3424fa1d49581d859b521
Source dataset
uspto-grants-2016_08
Patent number
US09409866B2

Reaction notes

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