Tetrabutylammonium Fluoride → HCID 44199465, compound

HRID 1254713Notes

Reaction equation

HRID 1254713 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 67006528HCID 67006528, compound

Product 1

HCID 44199465HCID 44199465, compoundYield 98.4%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

To a pre-cooled (−55° C.) solution of 4-((1R,2R)-2-(tert-butyldimethyl-silyloxy)-1-(5-(4-cyanophenyl)-1,3,4-oxadiazol-2-yl)propylamino)-2-(trifluoromethyl)benzo-nitrile (790 mg, 1.50 mmol) in THF (100 mL) was added TBAF (1.80 mL, 1.80 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 (100 mL). The resulting mixture was partitioned between H2O (50 mL) and EtOAc (200 mL). The aqueous layer was extracted with EtOAc (150 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 (50-80% EtOAc in hexanes) to provided the title compound as a colourless amorphous solid (610 mg, 98%): 1H NMR (400 MHz, acetone-d6, δ in ppm) 8.20 (dm, J=8.8 Hz, 2H), 8.00 (dm, J=8.8 Hz, 2H), 7.73 (d, J=8.6 Hz, 1H), 7.38 (d, J=2.4 Hz, 1H), 7.17 (dd, J=2.5, 8.8 Hz, 1H), 7.01 (d, J=8.8 Hz, 1H), 5.17 (dd, J=5.7, 8.8 Hz, 1H), 4.45 (pentet, J=6.1 Hz, 1H), 1.42 (d, J=6.4 Hz, 3H).

Workup

  1. additionUpon complete addition the reaction mixture
  2. customquenched with sat. aq. NH4Cl (100 mL)
  3. customThe resulting mixture was partitioned between H2O (50 mL) and EtOAc (200 mL)
  4. extractionThe aqueous layer was extracted with EtOAc (150 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 (50-80% EtOAc in hexanes)

Sources & evidence

ORD record
ord-fd65cf2e53864c9a9b97b66a526e2132
Source dataset
uspto-grants-2013_06
Patent number
US08455525B2

Reaction notes

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