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

HRID 470875Notes

Reaction equation

HRID 470875 reaction equation
[Si]([O:8][C@H:9]([CH3:39])[C@H:10]([C:22]1[O:26][C:25]([C:27]2[CH:32]=[CH:31][C:30]([NH:33][C:34](=[O:38])[CH2:35][CH2:36][CH3:37])=[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:28]=[CH:29][C:30]([NH:33][C:34](=[O:38])[CH2:35][CH2:36][CH3:37])=[CH:31][CH:32]=3)=[N:24][N:23]=2)[C@H:9]([OH:8])[CH3:39])[CH:17]=[CH:16][C:15]=1[C:18]#[N:19]

Participants

4

Reactant 2

HCID 2724141Tetrabutylammonium FluorideHCID 67006012N-(4-(5-((1R,2R)-2-(tert-Butyldimethylsilyloxy)-1-(3-chloro-4-cyano-2-methylphenylamino)propyl)-1,3,4-oxadiazol-2-yl)phenyl)butyramide

Product 1

HCID 44200058N-(4-(5-((1R,2R)-1-(3-Chloro-4-cyano-2-methylphenylamino)-2-hydroxypropyl)-1,3,4-oxadiazol-2-yl)phenyl)butyramideYield 97.4%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
10 °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)butyramide (352 mg, 0.62 mmol) in THF (25 mL) was added TBAF (0.74 mL, 0.74 mmol, 1 M solution in THF) over 5 minutes. Upon complete addition the reaction mixture was allowed to warm to 10° C. over 2.5 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 (35 mL). The combined organic extracts were dried (Na2SO4), filtered and concentrated under reduced pressure to provide a colourless oil, which was purified by flash chromatography over silica gel (50-100% EtOAc in hexanes) to provided the title compound as a colourless solid (274 mg, 97%): 1H NMR (400 MHz, d6-acetone, δ in ppm) 9.41 (s 1H), 7.91 (dm, J=9.0 Hz, 2H), 7.87 (dm, J=9.0 Hz, 2H), 7.49 (d, J=8.6 Hz, 1H), 6.89 (d, J=8.8 Hz, 1H), 5.86 (d, J=8.8 Hz, 1H), 5.04 (dd, J=5.5, 8.6 Hz, 1H), 4.69 (br s, 1H), 4.52 (pentet, J=5.9 Hz, 1H), 2.38 (t, J=7.2 Hz, 2H), 2.36 (s, 3H), 1.69 (sextet, J=7.2 Hz, 2H), 1.42 (d, J=6.5 Hz, 3H), 0.95 (t, J=7.4 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 (35 mL)
  5. dry with materialThe combined organic extracts were dried (Na2SO4)
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure
  8. customto provide a colourless oil, which
  9. customwas purified by flash chromatography over silica gel (50-100% EtOAc in hexanes)

Sources & evidence

ORD record
ord-b135d1e1b77d43c7b96e880ad8423e51
Source dataset
uspto-grants-2014_01
Patent number
US08629167B2

Reaction notes

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