Iodine → HCID 67005898, compound

HRID 2388418Notes

Reaction equation

HRID 2388418 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@@H:37]([CH3:64])[C@@H:38]([NH:53][C:54]1[CH:59]=[CH:58][C:57]([C:60]#[N:61])=[C:56]([Cl:62])[C:55]=1[CH3:63])[C:39]([NH:41][NH:42][C:43](=O)[C:44]1[CH:49]=[CH:48][C:47]([C:50]#[N:51])=[CH:46][CH:45]=1)=[O:40])([C:32]([CH3:35])([CH3:34])[CH3:33])([CH3:31])[CH3:30]>C(Cl)Cl.CCOC(C)=O>[Si:29]([O:36][C@@H:37]([CH3:64])[C@@H:38]([NH:53][C:54]1[CH:59]=[CH:58][C:57]([C:60]#[N:61])=[C:56]([Cl:62])[C:55]=1[CH3:63])[C:39]1[O:40][C:43]([C:44]2[CH:45]=[CH:46][C:47]([C:50]#[N:51])=[CH:48][CH:49]=2)=[N:42][N:41]=1)([C:32]([CH3:33])([CH3:35])[CH3:34])([CH3:30])[CH3:31]

Participants

7

Reactant 4

HCID 807IodineHCID 8471TriethylamineHCID 11776TriphenylphosphineHCID 67006940HCID 67006940, compound

Product 1

HCID 67005898HCID 67005898, compoundYield 84%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolvent2×HCID 8857Ethyl AcetateSolvent

Procedure

To a 1 L round bottom flask equipped with a magnetic stir bar and septum was added triphenylphosphine (12.3 g, 47.0 mmol) under an atmosphere of nitrogen. To this was added methylene chloride (500 mL) followed by addition of solid iodine (11.91 g, 47.0 mmol). This was allowed to stir at room temperature for a period of 10 min. then cooled to 0° C. Triethylamine (13.1 mL, 94 mmol) was then slowly added to this reaction (CAUTION: Exotherm). This mixture was allowed to stir at room temperature for an additional ten min., during which the reaction became a thick slurry. N′-((2R,3S)-3-(tert-butyldimethylsilyloxy)-2-(3-chloro-4-cyano-2-methylphenyl-amino)butanoyl)-4-cyanobenzohydrazide (12.35 g, 23.5 mmol) was taken up in methylene chloride (200 mL) and slowly added to the heavily stirred reaction mixture. After a period of 10 min, TLC (1:1 EtOAc:hexanes) showed product formation and no starting material. The reaction was then quenched by slow addition of 10% Na2S2O3/H2O (500 mL). The organic layer was then isolated and washed with additional 10% sodium thiosulfate/water (1×200 mL), brine (1×200 mL), then dried (Na2SO4). The solution was then filtered and concentrated under reduced pressure to reveal a brown oil/so lid. This was purified via silica gel chromatography eluted with 25% EtOAc/hexanes to provide the title compound as a white solid (9.98 g, 84%): 1H NMR (400 MHz, CDCl3, δ in ppm) (AA′XX′, J=8.8 Hz, 2H), 7.79 (AA′XX′, J=8.8 Hz, 2H), 7.33 (d, J=8.7 Hz, 1H), 6.44 (d, J=8.7 Hz, 1H), 5.35 (d, J=8.8 Hz, 1H), 4.82 (dd, J=2.0, 8.7 Hz, 1H), 3.54 (m, 1H), 2.37 (s, 3H), 1.42 (d, J=6.2 Hz, 3H), 0.85 (s, 9H), 0.07 (s, 3H), −0.22 (s, 3H).

Workup

  1. customTo a 1 L round bottom flask equipped with a magnetic stir bar
  2. temperaturethen cooled to 0° C
  3. stirringto stir at room temperature for an additional ten min., during which the reaction
  4. additionslowly added to the heavily stirred reaction mixture
  5. waitAfter a period of 10 min
  6. customThe reaction was then quenched by slow addition of 10% Na2S2O3/H2O (500 mL)
  7. customThe organic layer was then isolated
  8. washwashed with additional 10% sodium thiosulfate/water (1×200 mL), brine (1×200 mL)
  9. dry with materialdried (Na2SO4)
  10. filtrationThe solution was then filtered
  11. concentrationconcentrated under reduced pressure
  12. customThis was purified via silica gel chromatography
  13. washeluted with 25% EtOAc/hexanes

Sources & evidence

ORD record
ord-b1470ee37e8b4a7abca682778aa2fb7d
Source dataset
uspto-grants-2012_09
Patent number
US08268872B2

Reaction notes

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