Toluene → HCID 67189504, compound

HRID 546262Notes

Reaction equation

HRID 546262 reaction equation
[C:1](=[O:4])([O-])[O-].[K+].[K+].CC[C@@H]1[C@@H]2C[C@H]([C@@H](OC3C4C(=CC=CC=4)C(O[C@@H](C4C=CN=C5C=4C=C(OC)C=C5)[C@@H]4N5C[C@H](CC)[C@@H](CC5)C4)=NN=3)C3C=CN=C4C=3[CH:20]=[C:21]([O:28]C)[CH:22]=C4)N(CC2)C1.C1(C)C=CC=CC=1.[Cl:72][C:73]1[CH:74]=[C:75]([C@@H:83]([CH2:97][CH:98]2[CH2:102][CH2:101][CH2:100][CH2:99]2)[C:84]([NH:86][C:87]2[CH:91]=[CH:90][N:89]([CH2:92]C=C(C)C)[N:88]=2)=[O:85])[CH:76]=[CH:77][C:78]=1[S:79]([CH3:82])(=[O:81])=[O:80].CS(N)(=O)=O.S([O-])([O-])=O.[Na+].[Na+]>[Fe-3](C#N)(C#N)(C#N)(C#N)(C#N)C#N.[K+].[K+].[K+].[Os](=O)(=O)(=O)=O.O.C(OCC)(=O)C.O.C(O)(C)(C)C>[Cl:72][C:73]1[CH:74]=[C:75]([C@@H:83]([CH2:97][CH:98]2[CH2:99][CH2:100][CH2:101][CH2:102]2)[C:84]([NH:86][C:87]2[CH:91]=[CH:90][N:89]([CH2:92][CH:1]([OH:4])[C:21]([OH:28])([CH3:22])[CH3:20])[N:88]=2)=[O:85])[CH:76]=[CH:77][C:78]=1[S:79]([CH3:82])(=[O:81])=[O:80]

Participants

12

Reactant 6

HCID 1140TolueneHCID 11430Potassium CarbonateHCID 24437Sodium SulfiteHCID 72879MethanesulfonamideHCID 112172021,4-Bis(dihydroquinidine)phthalazineHCID 67188926HCID 67188926, compound

Product 1

HCID 67189504HCID 67189504, compound

Reagents, catalysts & solvents 5

HCID 30318Osmium TetroxideCatalystHCID 178511488HCID 178511488, compoundCatalystHCID 962WaterSolventHCID 8857Ethyl AcetateSolventHCID 714019492-Methylpropan-2-ol--water (1/1)Solvent

Conditions

Temperature
25 °C

Procedure

A mixture of potassium ferricyanide (0.06 mmol, 3.0 equiv.), potassium carbonate (0.06 mmol, 3.0 equiv.), and (DHQD)2PHAL (0.0006 mmol, 0.03 equiv.) is treated with a solution of water/tert-butyl alcohol (5 mL, 1:1) and is stirred at 25° C. for 5 min. The reaction mixture is treated with a 0.2 M solution of osmium tetroxide in toluene (0.0002 mmol, 0.01 equiv.) and cooled to 0° C. To this is added 2-(R)-(3-chloro-4-methanesulfonyl-phenyl)-3-cyclopentyl-N-[1-(3-methyl-but-2-enyl)-1H-pyrazol-3-yl]-propionamide (prepared as in Example 51, 0.02 mmol, 1 equiv.) and methane sulfonamide (0.02 equiv.). The heterogeneous mixture is stirred at 0° C. for 20 h. After such time the cooling bath is removed and the mixture is treated while stirring with ethyl acetate (15 mL) and sodium sulfite (0.36 mmol, 18 equiv.). To this solution is added water (20 mL) and the phases are separated. The aqueous phase is backextracted with ethyl acetate. The combined organic layers were dried over sodium sulfate, filtered, and concentrated in vacuo. Purification on an AnaLogix Intelliflash system would produce (R)-2-(3-chloro-4-methanesulfonyl-phenyl)-3-cyclopentyl-N-[1-(2,3-dihydroxy-3-methyl-butyl)-1H-pyrazol-3-yl]propionamide as a single diastereomer of unknown stereochemistry at the hydroxyl carbon center but opposite configuration at the hydroxyl stereocenter of Example 132.

Workup

  1. temperaturecooled to 0° C
  2. stirringThe heterogeneous mixture is stirred at 0° C. for 20 h
  3. customAfter such time the cooling bath is removed
  4. additionthe mixture is treated
  5. customthe phases are separated
  6. dry with materialThe combined organic layers were dried over sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. customPurification on an AnaLogix Intelliflash system

Sources & evidence

ORD record
ord-b34c3aeadcbc4f398f06907b28e888d1
Source dataset
uspto-grants-2011_05
Patent number
US07935699B2

Reaction notes

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