Iodine → HCID 67005760, compound

HRID 1254637Notes

Reaction equation

HRID 1254637 reaction equation
C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.II.C(N(CC)CC)C.[Si:29]([O:36][C:37]1[CH:38]=[C:39]([CH:68]=[CH:69][CH:70]=1)[C:40]([NH:42][NH:43][C:44](=[O:67])[C@H:45]([NH:56][C:57]1[CH:62]=[CH:61][C:60]([C:63]#[N:64])=[C:59](Cl)[C:58]=1C)[C@@H:46]([O:48][Si:49]([C:52]([CH3:55])([CH3:54])[CH3:53])([CH3:51])[CH3:50])[CH3:47])=O)([C:32]([CH3:35])([CH3:34])[CH3:33])([CH3:31])[CH3:30].[CH2:71]([Cl:73])Cl>>[Si:49]([O:48][C@@H:46]([CH3:47])[C@@H:45]([NH:56][C:57]1[CH:58]=[CH:59][C:60]([C:63]#[N:64])=[C:71]([Cl:73])[C:62]=1[CH3:61])[C:44]1[O:67][C:40]([C:39]2[CH:68]=[CH:69][CH:70]=[C:37]([O:36][Si:29]([C:32]([CH3:33])([CH3:34])[CH3:35])([CH3:30])[CH3:31])[CH:38]=2)=[N:42][N:43]=1)([C:52]([CH3:55])([CH3:53])[CH3:54])([CH3:50])[CH3:51]

Participants

6

Reactant 5

HCID 807IodineHCID 6344Dichloromethane2×HCID 8471TriethylamineHCID 11776TriphenylphosphineHCID 67006813HCID 67006813, compound

Product 1

HCID 67005760HCID 67005760, compoundYield 68%

Procedure

To a 25 mL round bottom flask equipped with a magnetic stir bar and septum was added triphenylphosphine (polymer bound, 3.0 mmol/g loading) (100 mg, 0.3 mmol) under an atmosphere of nitrogen. To this was added methylene chloride (3 mL) followed by addition of solid iodine (76 mg, 0.30 mmol). This was allowed to stir at room temperature for a period of 10 min followed by slow addition of triethylamine (0.17 mL, 1.2 mmol). This mixture was allowed to stir at room temperature for an additional ten min. 3-(tert-butyldimethylsilyloxy)-N′-((2R,3S)-3-(tert-butyldimethylsilyloxy)-2-(3-chloro-4-cyano-2-methylphenylamino)butanoyl)benzohydrazide (95 mg, 0.15 mmol) was taken up in methylene chloride (5 mL) and slowly added to the heavily stirred reaction mixture. After a period of 20 min, the solid polymer was filtered out and washed with additional methylene chloride (20 mL). The organic filtrate was then washed with 10% sodium thiosulfate/water (2×10 mL), brine (1×20 mL) and dried (Na2SO4). The solution was then filtered and concentrated under reduced to reveal a brown oil/solid, which was purified via silica gel chromatography eluted with 20% EtOAc/hexanes to provide the title compound as a white solid (63 mg, 68%): 1H NMR (400 MHz, CDCl3, δ in ppm) 7.52 (m, 1H), 7.38 (m, 1H), 7.33 (m, 2H), 6.99 (m, 1H), 6.46 (d, J=8.6 Hz, 1H), 5.37 (d, J=8.8 Hz, 1H), 4.80 (dd, J=1.8, 8.8 Hz, 1H), 4.54 (m, 1H), 2.37 (s, 3H), 1.42 (d, J=6.2 Hz, 3H), 0.98 (s, 9H), 0.86 (s, 9H), 0.19 (s, 6H), 0.06 (s, 3H), −0.20 (s, 3H).

Workup

  1. customTo a 25 mL round bottom flask equipped with a magnetic stir bar
  2. stirringto stir at room temperature for an additional ten min
  3. additionslowly added to the heavily stirred reaction mixture
  4. waitAfter a period of 20 min
  5. filtrationthe solid polymer was filtered out
  6. washwashed with additional methylene chloride (20 mL)
  7. washThe organic filtrate was then washed with 10% sodium thiosulfate/water (2×10 mL), brine (1×20 mL)
  8. dry with materialdried (Na2SO4)
  9. filtrationThe solution was then filtered
  10. concentrationconcentrated
  11. customwas purified via silica gel chromatography
  12. washeluted with 20% EtOAc/hexanes

Sources & evidence

ORD record
ord-2db1a9d077584ead955facdbd1eccdad
Source dataset
uspto-grants-2013_06
Patent number
US08455525B2

Reaction notes

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