Iodine → HCID 67006528, compound

HRID 1254712Notes

Reaction equation

HRID 1254712 reaction equation
[Si:1]([O:8][C@H:9]([CH3:38])[C@@H:10]([NH:25][C:26]1[CH:31]=[CH:30][C:29]([C:32]#[N:33])=[C:28]([C:34]([F:37])([F:36])[F:35])[CH:27]=1)[C:11]([NH:13][NH:14][C:15](=[O:24])[C:16]1[CH:21]=[CH:20][C:19]([C:22]#[N: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]([CH3:38])[C@@H:10]([NH:25][C:26]1[CH:31]=[CH:30][C:29]([C:32]#[N:33])=[C:28]([C:34]([F:36])([F:35])[F:37])[CH:27]=1)[C:11]1[O:24][C:15]([C:16]2[CH:21]=[CH:20][C:19]([C:22]#[N:23])=[CH:18][CH:17]=2)=[N:14][N:13]=1)([C:4]([CH3:5])([CH3:6])[CH3:7])([CH3:3])[CH3:2]

Participants

6

Reactant 4

HCID 807IodineHCID 8471TriethylamineHCID 11776TriphenylphosphineHCID 67006212HCID 67006212, compound

Product 1

HCID 67006528HCID 67006528, compoundYield 87%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A solution of N′-((2R,3R)-3-(tert-butyldimethylsilyl-oxy)-2-(4-cyano-3-(trifluoromethyl)phenylamino)butanoyl)-4-cyanobenzohydrazide (944 mg, 1.73 mmol) in CH2Cl2 (30 mL) was added to a pre-cooled (0° C.) mixture of PPh3 (907 mg, 3.46 mmol), iodine (878 mg, 3.46 mmol) and Et3N (0.96 mL, 6.92 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 (200 mL). The organic extract was washed with sat. aq. sodium thiosulfate (150 mL), dried (Na2SO4), filtered and concentrated under reduced pressure to provide a brown oil, which was purified by flash chromatography over silica gel (20-30% EtOAc in hexanes) to provide the title compound as a light yellow oil (790 mg, 87%): 1H NMR (400 MHz, acetone-d6, δ in ppm) 8.20 (dm, J=8.6 Hz, 2H), 8.03 (dm, J=8.8 Hz, 2H), 7.74 (d, J=8.8 Hz, 1H), 7.34 (d, J=2.4 Hz, 1H), 7.19 (dd, J=2.5, 8.8 Hz, 1H), 6.89 (d, J=9.0 Hz, 1H), 5.19 (dd, J=7.2, 9.0 Hz, 1H), 4.55 (dq, J=6.1, 7.2 Hz, 1H), 1.47 (d, J=6.1 Hz, 3H), 0.74 (s, 9H), 0.09 (s, 3H), −0.07 (s, 3H).

Workup

  1. temperaturea pre-cooled
  2. customquenched with sat. aq. sodium thiosulfate (200 mL)
  3. extractionThe solution was extracted with CH2Cl2 (200 mL)
  4. extractionThe organic extract
  5. washwas washed with sat. aq. sodium thiosulfate (150 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 (20-30% EtOAc in hexanes)

Sources & evidence

ORD record
ord-bc1b190ade7d4e77ad50de039320648e
Source dataset
uspto-grants-2013_06
Patent number
US08455525B2

Reaction notes

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