Iodine → 4-((1R,2R)-2-(tert-Butyldimethylsilyloxy)-1-(5-(4-(methylsulfonyl)phenyl)-1,3,4-oxadiazol-2-yl)propylamino)-2-(trifluoromethyl)benzonitrile

HRID 1254757Notes

Reaction equation

HRID 1254757 reaction equation
[Si:1]([O:8][C@H:9]([CH3:40])[C@@H:10]([NH:27][C:28]1[CH:33]=[CH:32][C:31]([C:34]#[N:35])=[C:30]([C:36]([F:39])([F:38])[F:37])[CH:29]=1)[C:11]([NH:13][NH:14][C:15](=[O:26])[C:16]1[CH:21]=[CH:20][C:19]([S:22]([CH3:25])(=[O:24])=[O:23])=[CH:18][CH:17]=1)=O)([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2].C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.II.CCN(CC)CC>C(Cl)Cl>[Si:1]([O:8][C@H:9]([CH3:40])[C@@H:10]([NH:27][C:28]1[CH:33]=[CH:32][C:31]([C:34]#[N:35])=[C:30]([C:36]([F:37])([F:39])[F:38])[CH:29]=1)[C:11]1[O:26][C:15]([C:16]2[CH:17]=[CH:18][C:19]([S:22]([CH3:25])(=[O:23])=[O:24])=[CH:20][CH:21]=2)=[N:14][N:13]=1)([C:4]([CH3:5])([CH3:7])[CH3:6])([CH3:2])[CH3:3]

Participants

6

Reactant 4

HCID 807IodineHCID 8471TriethylamineHCID 11776TriphenylphosphineHCID 67006087HCID 67006087, compound

Product 1

HCID 670062314-((1R,2R)-2-(tert-Butyldimethylsilyloxy)-1-(5-(4-(methylsulfonyl)phenyl)-1,3,4-oxadiazol-2-yl)propylamino)-2-(trifluoromethyl)benzonitrileYield 94.1%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A solution of N′-((2R,3R)-3-(tert-butyldimethylsilyloxy)-2-(4-cyano-3-(trifluoromethyl)phenylamino)butanoyl)-4-(methylsulfonyl)benzohydrazide (5.29 g, 8.80 mmol) in CH2Cl2 (250 mL) was added to a pre-cooled (0° C.) mixture of PPh3 (4.64 g, 17.7 mmol), iodine (4.48 g, 17.6 mmol) and Et3N (4.9 mL, 35.2 mmol). The reaction mixture was warmed to room temperature, stirred for 20 minutes and quenched with 10% sodium thiosulfate (100 mL). The organic extract was washed with 10% sodium thiosulfate (100 mL), H2O (100 mL), brine (50 mL), dried (Na2SO4), filtered and concentrated under reduced pressure to provide a pink foam, which was purified by flash chromatography over silica gel (50% EtOAc in hexanes) to provide the title compound (4.81 g, 94%), which was used directly in the next step.

Workup

  1. temperaturea pre-cooled
  2. customquenched with 10% sodium thiosulfate (100 mL)
  3. extractionThe organic extract
  4. washwas washed with 10% sodium thiosulfate (100 mL), H2O (100 mL), brine (50 mL)
  5. dry with materialdried (Na2SO4)
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure
  8. customto provide a pink foam, which
  9. customwas purified by flash chromatography over silica gel (50% EtOAc in hexanes)

Sources & evidence

ORD record
ord-1f06b85d0a934ba281f7ab48c983c489
Source dataset
uspto-grants-2013_06
Patent number
US08455525B2

Reaction notes

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