Iodine → 4-((1R,2R)-2-(tert-Butyldimethylsilyloxy)-1-(5-(4-nitrophenyl)-1,3,4-oxadiazol-2-yl)propylamino)-2-chloro-3-methylbenzonitrile

HRID 563332Notes

Reaction equation

HRID 563332 reaction equation
[Si:1]([O:8][C@H:9]([CH3:37])[C@@H:10]([NH:26][C:27]1[CH:32]=[CH:31][C:30]([C:33]#[N:34])=[C:29]([Cl:35])[C:28]=1[CH3:36])[C:11]([NH:13][NH:14][C:15](=[O:25])[C:16]1[CH:21]=[CH:20][C:19]([N+:22]([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]([CH3:37])[C@@H:10]([NH:26][C:27]1[CH:32]=[CH:31][C:30]([C:33]#[N:34])=[C:29]([Cl:35])[C:28]=1[CH3:36])[C:11]1[O:25][C:15]([C:16]2[CH:17]=[CH:18][C:19]([N+:22]([O-:24])=[O:23])=[CH:20][CH:21]=2)=[N:14][N:13]=1)([C:4]([CH3:7])([CH3:5])[CH3:6])([CH3:3])[CH3:2]

Participants

6

Reactant 4

HCID 807IodineHCID 8471TriethylamineHCID 11776TriphenylphosphineHCID 59193039N'-((2R,3R)-3-(tert-Butyldimethylsilyloxy)-2-(3-chloro-4-cyano-2-methylphenylamino)butanoyl)-4-nitrobenzohydrazide

Product 1

HCID 591930514-((1R,2R)-2-(tert-Butyldimethylsilyloxy)-1-(5-(4-nitrophenyl)-1,3,4-oxadiazol-2-yl)propylamino)-2-chloro-3-methylbenzonitrileYield 67%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A solution of N′-((2R,3R)-3-(tert-butyldimethylsilyloxy)-2-(3-chloro-4-cyano-2-methylphenylamino)butanoyl)-4-nitrobenzohydrazide (8.5 g, 15.57 mmol) in CH2Cl2 (250 mL) was added to a pre-cooled (0° C.) mixture of PPh3 (8.17 g, 31.13 mmol), iodine (7.90 g, 31.13 mmol) and Et3N (1.11 mL, 7.94 mmol). The reaction mixture was warmed to room temperature, stirred for 50 minutes and quenched with sat. aq. sodium thiosulfate (400 mL). The solution was extracted with CH2Cl2 (250 mL). The organic extract was washed with sat. aq. sodium thiosulfate (300 mL), dried (Na2SO4), filtered and concentrated under reduced pressure to provide a brown oil, which was purified by flash chromatography over silica gel (20-40% EtOAc in hexanes) to provide the title compound as a light yellow solid (5.5 g, 67%): 1H NMR (400 MHz, CDCl3, δ in ppm) 8.37 (dm, J=9.0 Hz, 2H), 8.18 (dm, J=9.0 Hz, 2H), 7.36 (d, J=8.6 Hz, 1H), 6.61 (d, J=8.6 Hz, 1H), 5.11 (d, J=9.2 Hz, 1H), 4.87 (dd, J=3.9, 8.8 Hz, 1H), 4.46 (dq, J=3.7, 6.3 Hz, 1H), 2.34 (s, 3H), 1.31 (d, J=6.3 Hz, 3H), 0.93 (s, 9H), 0.15 (s, 3H), 0.12 (s, 3H).

Workup

  1. temperaturea pre-cooled
  2. customquenched with sat. aq. sodium thiosulfate (400 mL)
  3. extractionThe solution was extracted with CH2Cl2 (250 mL)
  4. extractionThe organic extract
  5. washwas washed with sat. aq. sodium thiosulfate (300 mL)
  6. dry with materialdried (Na2SO4)
  7. filtrationfiltered
  8. concentrationconcentrated under reduced pressure
  9. customto provide a brown oil, which
  10. customwas purified by flash chromatography over silica gel (20-40% EtOAc in hexanes)

Sources & evidence

ORD record
ord-1467f8e781304955b9429c603e64397b
Source dataset
uspto-grants-2011_11
Patent number
US08067448B2

Reaction notes

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