Tetrabutylammonium Fluoride → HCID 59193064, compound

HRID 2388549Notes

Reaction equation

HRID 2388549 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 59193043HCID 59193043, compound

Product 1

HCID 59193064HCID 59193064, compoundYield 11.2%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a pre-cooled (−55° C.) solution of N-(4-(5-((1R,2S)-2-(tert-butyldimethylsilyloxy)-1-(3-chloro-4-cyano-2-methylphenylamino)propyl)-1,3,4-oxadiazol-2-yl)phenyl)benzamide (100 mg, 0.17 mmol) in THF (10 mL) was added TBAF (20 μL, 0.20 mmol, 1 M solution in THF) over 5 minutes. Upon complete addition the reaction mixture was allowed to warm to room temperature over 1.5 h and stirred for a further 20 minutes before being quenched with sat. aq. NH4Cl (10 mL). The resulting mixture was partitioned between H2O (15 mL) and EtOAc (25 mL). The aqueous layer was extracted with EtOAc (25 mL). The combined organic extracts were dried (Na2SO4), filtered and concentrated under reduced pressure to provide a pale yellow oil, which was purified by flash chromatography over silica gel (60-100% EtOAc in hexanes) to provided the title compound as a colourless solid (9.3 mg, 11%): 1H NMR (400 MHz, d6-acetone, δ in ppm) 9.86 (s 1H), 8.09-7.91 (m, 6H), 7.64-7.42 (m, 4H), 6.88 (d, J=8.8 Hz, 1H), 5.69 (d, J=6.6 Hz, 1H), 5.11 (dd, J=3.7, 8.2 Hz, 1H), 4.83 (br s, 1H), 4.62 (dq, J=3.5, 5.9 Hz, 1H), 2.41 (s, 3H), 1.41 (d, J=6.3 Hz, 3H).

Workup

  1. additionUpon complete addition the reaction mixture
  2. custombefore being quenched with sat. aq. NH4Cl (10 mL)
  3. customThe resulting mixture was partitioned between H2O (15 mL) and EtOAc (25 mL)
  4. extractionThe aqueous layer was extracted with EtOAc (25 mL)
  5. dry with materialThe combined organic extracts were dried (Na2SO4)
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure
  8. customto provide a pale yellow oil, which
  9. customwas purified by flash chromatography over silica gel (60-100% EtOAc in hexanes)

Sources & evidence

ORD record
ord-aca0af5b0e1148928d211691b80d6226
Source dataset
uspto-grants-2012_09
Patent number
US08268872B2

Reaction notes

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