4-Phenylpyridine-1-oxide → HCID 58920674, compound

HRID 1365547Notes

Reaction equation

HRID 1365547 reaction equation
[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([C@@:8]([NH:30][C:31](=[O:42])[CH:32]=[C:33]([C:38]([F:41])([F:40])[F:39])[C:34]([F:37])([F:36])[F:35])([C:16]2[CH:21]=[C:20]([O:22][C:23]([F:28])([F:27])[CH:24]([F:26])[F:25])[CH:19]=[C:18]([F:29])[CH:17]=2)[CH2:9][C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=2)=[N:6][CH:7]=1.C1(C2C=C[N+]([O-:55])=CC=2)C=CC=CC=1.[O-]Cl.[Na+]>C(#N)C>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([C@@:8]([NH:30][C:31]([CH:32]2[C:33]([C:38]([F:39])([F:41])[F:40])([C:34]([F:35])([F:36])[F:37])[O:55]2)=[O:42])([C:16]2[CH:21]=[C:20]([O:22][C:23]([F:27])([F:28])[CH:24]([F:26])[F:25])[CH:19]=[C:18]([F:29])[CH:17]=2)[CH2:9][C:10]2[CH:11]=[CH:12][CH:13]=[CH:14][CH:15]=2)=[N:6][CH:7]=1

Participants

5

Reactant 3

HCID 708034-Phenylpyridine-1-oxideHCID 23665760Sodium HypochloriteHCID 58920018HCID 58920018, compound

Product 1

HCID 58920674HCID 58920674, compoundYield 92%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Conditions

Temperature
0 °C

Procedure

At 0° C., to a solution of (S)-N-(1-(5-chloropyridin-2-yl)-1-(3-fluoro-5-(1,1,2,2-tetrafluoroethoxy)phenyl)-2-phenylethyl)-4,4,4-trifluoro-3-(trifluoromethyl)but-2-enamide (260 mg, 0.41 mmol) and 4-phenyl pyridine N-oxide (56 mg, 0.33 mmol) in acetonitrile (16 mL) was added NaOCl solution (363 uL, chlorine wt % 10-3%, 1.23 mmol). The reaction mixture was stirred at 0° C. for 10 min, then at room temperature for 1 h. After removal of the solvents in vacuo the residue was diluted with EtOAc (30 mL) and the solution washed with saturated Na2SO3 (30 mL), dried over MgSO4, filtered and concentrated. The residue was purified by ISCO chromatography (40 g column, flow rate 20 mL/min) using hexanes/EtOAc (0-10% over 30 min) to give N-((S)-1-(5-chloropyridin-2-yl)-1-(3-fluoro-5-(1,1,2,2-tetrafluoroethoxy)phenyl)-2-phenylethyl)-3,3-bis(trifluoromethyl)oxirane-2-carboxamide as a diastereomer mixture at a retention time of 27-35 min (243.9 mg, 92% yield). The diastereomeric mixture was separated by Chiral preparative HPLC chiralpak AD 20μ column, 5×50 cm, eluting with 10% IPA/Heptane with flow rate 50 mL/min.

Workup

  1. waitat room temperature for 1 h
  2. customAfter removal of the solvents in vacuo the residue
  3. additionwas diluted with EtOAc (30 mL)
  4. washthe solution washed with saturated Na2SO3 (30 mL)
  5. dry with materialdried over MgSO4
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe residue was purified by ISCO chromatography (40 g column, flow rate 20 mL/min)
  9. customhexanes/EtOAc (0-10% over 30 min)

Sources & evidence

ORD record
ord-53000a4e9bfb444e9a428ef0aa62b740
Source dataset
uspto-grants-2011_02
Patent number
US07888376B2

Reaction notes

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