Iodine → 4-((1R,2S)-2-(tert-Butyldimethylsilyloxy)-1-(5-(4-(methylsulfonyl)phenyl)-1,3,4-oxadiazol-2-yl)propylamino)-2-chlorobenzonitrile

HRID 563277Notes

Reaction equation

HRID 563277 reaction equation
C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.II.[Si:22]([O:29][C@@H:30]([CH3:58])[C@@H:31]([NH:48][C:49]1[CH:54]=[CH:53][C:52]([C:55]#[N:56])=[C:51]([Cl:57])[CH:50]=1)[C:32]([NH:34][NH:35][C:36](=[O:47])[C:37]1[CH:42]=[CH:41][C:40]([S:43]([CH3:46])(=[O:45])=[O:44])=[CH:39][CH:38]=1)=O)([C:25]([CH3:28])([CH3:27])[CH3:26])([CH3:24])[CH3:23]>C(Cl)Cl>[Si:22]([O:29][C@@H:30]([CH3:58])[C@@H:31]([NH:48][C:49]1[CH:54]=[CH:53][C:52]([C:55]#[N:56])=[C:51]([Cl:57])[CH:50]=1)[C:32]1[O:47][C:36]([C:37]2[CH:38]=[CH:39][C:40]([S:43]([CH3:46])(=[O:45])=[O:44])=[CH:41][CH:42]=2)=[N:35][N:34]=1)([C:25]([CH3:26])([CH3:28])[CH3:27])([CH3:24])[CH3:23]

Participants

5

Reactant 3

HCID 807IodineHCID 11776TriphenylphosphineHCID 58433612N'-((2R,3S)-3-(tert-Butyldimethylsilyloxy)-2-(3-chloro-4-cyanophenylamino)butanoyl)-4-(methylsulfonyl)benzohydrazide

Product 1

HCID 584336564-((1R,2S)-2-(tert-Butyldimethylsilyloxy)-1-(5-(4-(methylsulfonyl)phenyl)-1,3,4-oxadiazol-2-yl)propylamino)-2-chlorobenzonitrileYield 95%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

Polymer supported triphenylphosphine (2.08 g, 6.24 mmol) was dilluted in 200 ml of DCM followed by addition of I2 (1.58 g, 6.24 mmol) and TEA (2.31 mL, 16.64 mmol) at 0° C. N′-((2R,3S)-3-(tert-butyldimethylsilyloxy)-2-(3-chloro-4-cyanophenylamino)butanoyl)-4-(methylsulfonyl)benzohydrazide (2.35 g, 4.16 mmol) in 200 mL DCM was added to the pre-cooled solution mixture of PPh3/I2/TEA system and stirred. The temperature was allowed to warm to room temperature and stirred for an additional 10 min. The reaction was quenched with 55 mL saturated sodium thiosulfate and the biphasic mixture was separated. The aqueous layer was extracted with EtOAc (3×70 mL) and the combined organic extracts were dried (Na2SO4), filtered and concentrated under reduced pressure. The resulting crude oil was purified by flash chromatography (SiO2) [EtOAc-hexanes (1:2), then (1:1) as eluent] to provide the title compound (2.16 g, 95%). The crude material was used directly in the next step.

Workup

  1. stirringstirred for an additional 10 min
  2. customThe reaction was quenched with 55 mL saturated sodium thiosulfate
  3. customthe biphasic mixture was separated
  4. extractionThe aqueous layer was extracted with EtOAc (3×70 mL)
  5. dry with materialthe combined organic extracts were dried (Na2SO4)
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure
  8. customThe resulting crude oil was purified by flash chromatography (SiO2) [EtOAc-hexanes (1:2)

Sources & evidence

ORD record
ord-9f6c70075dd640c2bdfc99d617688fb5
Source dataset
uspto-grants-2011_11
Patent number
US08067448B2

Reaction notes

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