Iodine → 4-((1R,2S)-2-(tert-Butyldimethylsilyloxy)-1-(5-(4-cyanophenyl)-1,3,4-oxadiazol-2-yl)propyl-amino)-2-(trifluoromethyl)benzonitrile

HRID 1254715Notes

Reaction equation

HRID 1254715 reaction equation
[C:1]([Si:5]([CH3:38])([CH3:37])[O:6][C@@H:7]([CH3:36])[C@@H:8]([NH:23][C:24]1[CH:29]=[CH:28][C:27]([C:30]#[N:31])=[C:26]([C:32]([F:35])([F:34])[F:33])[CH:25]=1)[C:9]([NH:11][NH:12][C:13](=O)[C:14]1[CH:19]=[CH:18][C:17]([C:20]#[N:21])=[CH:16][CH:15]=1)=[O:10])([CH3:4])([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:5]([O:6][C@@H:7]([CH3:36])[C@@H:8]([NH:23][C:24]1[CH:29]=[CH:28][C:27]([C:30]#[N:31])=[C:26]([C:32]([F:33])([F:35])[F:34])[CH:25]=1)[C:9]1[O:10][C:13]([C:14]2[CH:15]=[CH:16][C:17]([C:20]#[N:21])=[CH:18][CH:19]=2)=[N:12][N:11]=1)([C:1]([CH3:4])([CH3:3])[CH3:2])([CH3:38])[CH3:37]

Participants

6

Reactant 4

HCID 807IodineHCID 8471TriethylamineHCID 11776TriphenylphosphineHCID 67006853HCID 67006853, compound

Product 1

HCID 670061474-((1R,2S)-2-(tert-Butyldimethylsilyloxy)-1-(5-(4-cyanophenyl)-1,3,4-oxadiazol-2-yl)propyl-amino)-2-(trifluoromethyl)benzonitrileYield 89%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A solution of N′-((2R,3S)-3-(tert-butyldimethyl-silyloxy)-2-(4-cyano-3-(trifluoromethyl)phenylamino)butanoyl)-4-cyanobenzohydrazide (1.05 g, 1.92 mmol) in CH2Cl2 (40 mL) was added to a pre-cooled (0° C.) mixture of PPh3 (1.01 g, 3.85 mmol), iodine (980 mg, 3.85 mmol) and Et3N (1.1 mL, 7.70 mmol). The reaction mixture was warmed to room temperature, stirred for 30 min and quenched with sat. aq. sodium thiosulfate (200 mL). The solution was extracted with CH2Cl2 (150 mL). The organic extract was washed with sat. aq. sodium thiosulfate (100 mL), dried (Na2SO4), filtered and concentrated under reduced pressure to provide a light brown solid, which was purified by flash chromatography over silica gel (50% EtOAc in hexanes) to provide the title compound as a light yellow oil (900 mg, 89%): 1H NMR (400 MHz, acetone-d6, δ in ppm) 8.22 (dm, J=8.8 Hz, 2H), 8.02 (dm, J=8.8 Hz, 2H), 7.72 (d, J=8.8 Hz, 1H), 7.41 (d, J=2.5 Hz, 1H), 7.17 (dd, J=2.3, 8.6 Hz, 1H), 6.75 (d, J=9.2 Hz, 1H), 5.36 (dd, J=3.3, 9.4 Hz, 1H), 4.73 (dq, J=3.1, 6.1 Hz, 1H), 1.45 (d, J=6.3 Hz, 3H), 0.78 (s, 9H), 0.07 (s, 3H), −0.13 (s, 3H

Workup

  1. temperaturea pre-cooled
  2. customquenched with sat. aq. sodium thiosulfate (200 mL)
  3. extractionThe solution was extracted with CH2Cl2 (150 mL)
  4. extractionThe organic extract
  5. washwas washed with sat. aq. sodium thiosulfate (100 mL)
  6. dry with materialdried (Na2SO4)
  7. filtrationfiltered
  8. concentrationconcentrated under reduced pressure
  9. customto provide a light brown solid, which
  10. customwas purified by flash chromatography over silica gel (50% EtOAc in hexanes)

Sources & evidence

ORD record
ord-3118292846344bd7a47e314bcde5f4a7
Source dataset
uspto-grants-2013_06
Patent number
US08455525B2

Reaction notes

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