Hydrogen Peroxide → Odanacatib

HRID 1880519Notes

Reaction equation

HRID 1880519 reaction equation
[C:1]([C:3]1([NH:6][C:7](=[O:34])[C@H:8]([CH2:29][C:30]([F:33])([CH3:32])[CH3:31])[NH:9][C@@H:10]([C:15]2[CH:20]=[CH:19][C:18]([C:21]3[CH:26]=[CH:25][C:24](SC)=[CH:23][CH:22]=3)=[CH:17][CH:16]=2)[C:11]([F:14])([F:13])[F:12])[CH2:5][CH2:4]1)#[N:2].OO.[S:37]([O-:41])([O-])(=[O:39])=S.[Na+].[Na+].[C:44](OCC)(=O)C>C1(C)C=CC=CC=1.ClCCl.[N+](CCCC)(CCCC)(CCCC)CCCC.[O-]S(O)(=O)=O>[C:1]([C:3]1([NH:6][C:7](=[O:34])[C@H:8]([CH2:29][C:30]([F:33])([CH3:31])[CH3:32])[NH:9][C@@H:10]([C:15]2[CH:16]=[CH:17][C:18]([C:21]3[CH:22]=[CH:23][C:24]([S:37]([CH3:44])(=[O:41])=[O:39])=[CH:25][CH:26]=3)=[CH:19][CH:20]=2)[C:11]([F:12])([F:13])[F:14])[CH2:4][CH2:5]1)#[N:2]

Participants

8

Reactant 4

HCID 784Hydrogen PeroxideHCID 8857Ethyl AcetateHCID 24477Sodium ThiosulfateHCID 11496895HCID 11496895, compound

Product 1

HCID 10152654Odanacatib

Reagents, catalysts & solvents 3

HCID 94433Tetrabutylammonium hydrogen sulfateCatalystHCID 1140TolueneSolventHCID 6344DichloromethaneSolvent

Procedure

To a 0° solution of the sulfide (0.265 g) from Step 10 in toluene (5 mL) and dichloromethane (5 mL) was added Na2WO4.2H2O (0.002 g) and n-Bu4NHSO4 (0.01 g). 30% Hydrogen peroxide (0.137 mL) was then slowly added and the mixture was stirred at room temperature for 3 hours. The mixture was poured slowly onto a mixture of ice, dilute aqueous sodium thiosulfate and ethyl acetate. The organic layer was separated and the aqueous further extracted with ethyl acetate. The combined organic layers were washed with brine, dried with magnesium sulfate and the solvent was removed in vacuo to yield a residue which was purified on SiO2 using ethyl acetate, hexanes and dichloromethane (1:1:0.1) as eluant. The residue was triturated in diethyl ether to yield N1-(1-cyanocyclopropyl)-4-fluoro-N2-{(1S)-2,2,2-trifluoro-1-[4′-(methyl sulfonyl)-1,1′-biphenyl-4-yl]ethyl}-L-leucinamide.

Workup

  1. customThe organic layer was separated
  2. extractionthe aqueous further extracted with ethyl acetate
  3. washThe combined organic layers were washed with brine
  4. dry with materialdried with magnesium sulfate
  5. customthe solvent was removed in vacuo
  6. customto yield a residue which
  7. customwas purified on SiO2
  8. customThe residue was triturated in diethyl ether

Sources & evidence

ORD record
ord-b9c434d925294a4b8a201f0460de8fdf
Source dataset
uspto-grants-2012_11
Patent number
US08318748B2

Reaction notes

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