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

HRID 1254748Notes

Reaction equation

HRID 1254748 reaction equation
C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.CCN(CC)CC.[Br:27][C:28]1[CH:61]=[CH:60][C:31]([C:32]([NH:34][NH:35][C:36](=[O:59])[C@H:37]([NH:48][C:49]2[CH:54]=[CH:53][C:52]([C:55]#[N:56])=[C:51]([Cl:57])[C:50]=2[CH3:58])[C@@H:38]([O:40][Si:41]([C:44]([CH3:47])([CH3:46])[CH3:45])([CH3:43])[CH3:42])[CH3:39])=O)=[CH:30][CH:29]=1>C(Cl)Cl>[Br:27][C:28]1[CH:29]=[CH:30][C:31]([C:32]2[O:59][C:36]([C@H:37]([NH:48][C:49]3[CH:54]=[CH:53][C:52]([C:55]#[N:56])=[C:51]([Cl:57])[C:50]=3[CH3:58])[C@@H:38]([O:40][Si:41]([C:44]([CH3:46])([CH3:47])[CH3:45])([CH3:42])[CH3:43])[CH3:39])=[N:35][N:34]=2)=[CH:60][CH:61]=1

Participants

5

Reactant 3

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 12 (4.1 g, 16.2 mmol) at 0° C. After 12 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. dissolutionAfter 12 was dissolved completely
  2. customThe reaction was quenched with saturated sodium thiosulfate (50 mL)
  3. additiondiluted with DCM (400 mL)
  4. customThe organic layer was separated
  5. washwashed with water, brine
  6. dry with materialdried over Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customThe resulting residue was purified by flash chromatography

Sources & evidence

ORD record
ord-e4ac84145c84470fa87a75e3c6237acb
Source dataset
uspto-grants-2013_06
Patent number
US08455525B2

Reaction notes

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