Tetrabutylammonium Fluoride → N-(4-(5-((1R,2R)-1-(3-Chloro-4-cyano-2-methylphenylamino)-2-hydroxypropyl)-1,3,4-oxadiazol-2-yl)phenyl)benzamide

HRID 1254784Notes

Reaction equation

HRID 1254784 reaction equation
[Si]([O:8][C@H:9]([CH3:42])[C@H:10]([C:22]1[O:26][C:25]([C:27]2[CH:32]=[CH:31][C:30]([NH:33][C:34](=[O:41])[C:35]3[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=3)=[CH:29][CH:28]=2)=[N:24][N:23]=1)[NH:11][C:12]1[CH:17]=[CH:16][C:15]([C:18]#[N:19])=[C:14]([Cl:20])[C:13]=1[CH3:21])(C(C)(C)C)(C)C.CCCC[N+](CCCC)(CCCC)CCCC.[F-]>C1COCC1>[Cl:20][C:14]1[C:13]([CH3:21])=[C:12]([NH:11][C@@H:10]([C:22]2[O:26][C:25]([C:27]3[CH:32]=[CH:31][C:30]([NH:33][C:34](=[O:41])[C:35]4[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=4)=[CH:29][CH:28]=3)=[N:24][N:23]=2)[C@H:9]([OH:8])[CH3:42])[CH:17]=[CH:16][C:15]=1[C:18]#[N:19]

Participants

4

Reactant 2

HCID 2724141Tetrabutylammonium FluorideHCID 59193025N-(4-(5-((1R,2R)-2-(tert-Butyldimethylsilyloxy)-1-(3-chloro-4-cyano-2-methylphenylamino)propyl)-1,3,4-oxadiazol-2-yl)phenyl)benzamide

Product 1

HCID 44199942N-(4-(5-((1R,2R)-1-(3-Chloro-4-cyano-2-methylphenylamino)-2-hydroxypropyl)-1,3,4-oxadiazol-2-yl)phenyl)benzamideYield 91%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
13 °C

Procedure

To a pre-cooled (−55° C.) solution of N-(4-(5-((1R,2R)-2-(tert-butyldimethylsilyloxy)-1-(3-chloro-4-cyano-2-methylphenylamino)propyl)-1,3,4-oxadiazol-2-yl)phenyl)benzamide (367 mg, 0.61 mmol) in THF (25 mL) was added TBAF (0.73 mL, 0.73 mmol, 1 M solution in THF) over 5 minutes. Upon complete addition the reaction mixture was allowed to warm to 13° C. over 3.5 h and quenched with sat. aq. NH4Cl (30 mL). The resulting mixture was partitioned between H2O (30 mL) and EtOAc (40 mL). The aqueous layer was extracted with EtOAc (30 mL). The combined organic extracts were dried (Na2SO4), filtered and concentrated under reduced pressure to provide a yellow oil, which was purified by flash chromatography over silica gel (20-60% EtOAc in hexanes) to provided the title compound as a colourless solid (270 mg, 91%): 1H NMR (400 MHz, d6-acetone, δ in ppm) 9.83 (s 1H), 8.08-7.95 (m, 6H), 7.63-7.47 (m, 4H), 6.90 (d, J=8.6 Hz, 1H), 5.88 (d, J=8.8 Hz, 1H), 5.06 (dd, J=5.5, 8.8 Hz, 1H), 4.68 (br s, 1H), 4.53 (pentet, J=6.1 Hz, 1H), 2.37 (s, 3H), 1.43 (d, J=6.5 Hz, 3H).

Workup

  1. additionUpon complete addition the reaction mixture
  2. customquenched with sat. aq. NH4Cl (30 mL)
  3. customThe resulting mixture was partitioned between H2O (30 mL) and EtOAc (40 mL)
  4. extractionThe aqueous layer was extracted with EtOAc (30 mL)
  5. dry with materialThe combined organic extracts were dried (Na2SO4)
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure
  8. customto provide a yellow oil, which
  9. customwas purified by flash chromatography over silica gel (20-60% EtOAc in hexanes)

Sources & evidence

ORD record
ord-c20b9403b2cb41ab8332dcaaa93327f7
Source dataset
uspto-grants-2013_06
Patent number
US08455525B2

Reaction notes

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