Iodine → 4-((1R,2S)-1-(5-(4-Bromophenyl)-1,3,4-oxadiazol-2-yl)-2-(tert-butyldimethylsilyloxy)propylamino)-2-chloro-3-methylbenzonitrile

HRID 470842Notes

Reaction equation

HRID 470842 reaction equation
C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.II.CCN(CC)CC.[Br:29][C:30]1[CH:63]=[CH:62][C:33]([C:34]([NH:36][NH:37][C:38](=[O:61])[C@H:39]([NH:50][C:51]2[CH:56]=[CH:55][C:54]([C:57]#[N:58])=[C:53]([Cl:59])[C:52]=2[CH3:60])[C@@H:40]([O:42][Si:43]([C:46]([CH3:49])([CH3:48])[CH3:47])([CH3:45])[CH3:44])[CH3:41])=O)=[CH:32][CH:31]=1>C(Cl)Cl>[Br:29][C:30]1[CH:31]=[CH:32][C:33]([C:34]2[O:61][C:38]([C@H:39]([NH:50][C:51]3[CH:56]=[CH:55][C:54]([C:57]#[N:58])=[C:53]([Cl:59])[C:52]=3[CH3:60])[C@@H:40]([O:42][Si:43]([C:46]([CH3:48])([CH3:49])[CH3:47])([CH3:44])[CH3:45])[CH3:41])=[N:37][N:36]=2)=[CH:62][CH:63]=1

Participants

6

Reactant 4

HCID 807Iodine2×HCID 8471TriethylamineHCID 11776TriphenylphosphineHCID 670067824-Bromo-N'-((2R,3S)-3-(tert-butyldimethylsilyloxy)-2-(3-chloro-4-cyano-2-methylphenylamino)butanoyl)benzohydrazide

Product 1

HCID 670062614-((1R,2S)-1-(5-(4-Bromophenyl)-1,3,4-oxadiazol-2-yl)-2-(tert-butyldimethylsilyloxy)propylamino)-2-chloro-3-methylbenzonitrileYield 89%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To a solution of triphenylphosphine (4.23 g, 16.1 mmol) in DCM (200 mL) was added I2 (4.1 g, 16.2 mmol) at 0° C. After I2 was dissolved completely, Et3N (4.5 mL, 32.3 mmol) was added, followed by a solution of 4-bromo-N′-((2R,3S)-3-(tert-butyldimethylsilyloxy)-2-(3-chloro-4-cyano-2-methylphenylamino)butanoyl)-benzohydrazide (4.68 g, 8.1 mmol) in DCM (100 mL). The reaction mixture was allowed to warm to room temperature and stirred for additional 15 min. The reaction was quenched with saturated sodium thiosulfate (50 mL) and diluted with DCM (400 mL). The organic layer was separated and washed with water, brine, dried over Na2SO4, filtered and concentrated. The resulting residue was purified by flash chromatography to provide the title compound (4.03 g, 89%), which was used directly in the next step

Workup

  1. customThe reaction was quenched with saturated sodium thiosulfate (50 mL)
  2. additiondiluted with DCM (400 mL)
  3. customThe organic layer was separated
  4. washwashed with water, brine
  5. dry with materialdried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe resulting residue was purified by flash chromatography

Sources & evidence

ORD record
ord-434b277cc3894ef8929b29114238857a
Source dataset
uspto-grants-2014_01
Patent number
US08629167B2

Reaction notes

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