Tetrabutylammonium Fluoride → HCID 44199466, compound

HRID 470811Notes

Reaction equation

HRID 470811 reaction equation
C([Si](C)(C)[O:6][C@@H:7]([CH3:35])[C@@H:8]([NH:22][C:23]1[CH:30]=[CH:29][C:26]([C:27]#[N:28])=[C:25]([C:31]([F:34])([F:33])[F:32])[CH:24]=1)[C:9]1[O:10][C:11]([C:14]2[CH:19]=[CH:18][C:17]([C:20]#[N:21])=[CH:16][CH:15]=2)=[N:12][N:13]=1)(C)(C)C.CCCC[N+](CCCC)(CCCC)CCCC.[F-]>C1COCC1>[C:20]([C:17]1[CH:16]=[CH:15][C:14]([C:11]2[O:10][C:9]([C@H:8]([NH:22][C:23]3[CH:30]=[CH:29][C:26]([C:27]#[N:28])=[C:25]([C:31]([F:32])([F:34])[F:33])[CH:24]=3)[C@@H:7]([OH:6])[CH3:35])=[N:13][N:12]=2)=[CH:19][CH:18]=1)#[N:21]

Participants

4

Reactant 2

HCID 2724141Tetrabutylammonium FluorideHCID 670061474-((1R,2S)-2-(tert-Butyldimethylsilyloxy)-1-(5-(4-cyanophenyl)-1,3,4-oxadiazol-2-yl)propyl-amino)-2-(trifluoromethyl)benzonitrile

Product 1

HCID 44199466HCID 44199466, compoundYield 86.8%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

To a pre-cooled (−55° C.) solution of 4-((1R,2S)-2-(tert-butyldimethyl-silyloxy)-1-(5-(4-cyanophenyl)-1,3,4-oxadiazol-2-yl)propylamino)-2-(trifluoromethyl)benzo-nitrile (900 mg, 1.17 mmol) in THF (120 mL) was added TBAF (2.05 mL, 2.05 mmol, 1 M solution in THF) over 10 min. Upon complete addition the reaction mixture was allowed to warm to 0° C. over 1 h, then stirred at 0° C. for a further 30 min and quenched with sat. aq. NH4Cl (150 mL). The resulting mixture was partitioned between H2O (150 mL) and EtOAc (250 mL). The aqueous layer was extracted with EtOAc (100 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 (30-50% EtOAc in hexanes) to provided the title compound as a colourless oil (420 mg, 66%): 1H NMR (400 MHz, acetone-d6, δ in ppm) 8.20 (dm, J=8.8 Hz, 2 H), 8.01 (dm, J=8.8 Hz, 2H), 7.73 (d, J=8.6 Hz, 1H), 7.46 (d, J=2.4 Hz, 1H), 7.20 (dd, J=2.5, 8.8 Hz, 1H), 6.84 (d, J=8.8 Hz, 1H), 5.23 (dd, J=3.5, 8.8 Hz, 1H), 4.62 (dq, J=3.5, 6.5 Hz, 1H), 1.40 (d, J=6.3 Hz, 3H).

Workup

  1. additionUpon complete addition the reaction mixture
  2. customquenched with sat. aq. NH4Cl (150 mL)
  3. customThe resulting mixture was partitioned between H2O (150 mL) and EtOAc (250 mL)
  4. extractionThe aqueous layer was extracted with EtOAc (100 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 (30-50% EtOAc in hexanes)

Sources & evidence

ORD record
ord-a22262785de44d6aa9e2f7899f2dfd5c
Source dataset
uspto-grants-2014_01
Patent number
US08629167B2

Reaction notes

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