Tetrabutylammonium Fluoride → HCID 44199464, compound

HRID 563259Notes

Reaction equation

HRID 563259 reaction equation
[Si]([O:8][C@@H:9]([CH3:28])[C@@H:10]([NH:17][C:18]1[CH:25]=[CH:24][C:21]([C:22]#[N:23])=[C:20]([Cl:26])[C:19]=1[CH3:27])[C:11]1[O:12][C:13]([CH3:16])=[N:14][N:15]=1)(C(C)(C)C)(C)C.CCCC[N+](CCCC)(CCCC)CCCC.[F-]>C1COCC1>[Cl:26][C:20]1[C:19]([CH3:27])=[C:18]([NH:17][C@@H:10]([C:11]2[O:12][C:13]([CH3:16])=[N:14][N:15]=2)[C@@H:9]([OH:8])[CH3:28])[CH:25]=[CH:24][C:21]=1[C:22]#[N:23]

Participants

4

Reactant 2

HCID 2724141Tetrabutylammonium FluorideHCID 67006780HCID 67006780, compound

Product 1

HCID 44199464HCID 44199464, compoundYield 95%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

To a pre-cooled (−45° C.) solution of 4-((1R,2S)-2-(tert-butyldimethylsilyloxy)-1-(5-methyl-1,3,4-oxadiazol-2-yl)propylamino)-2-chloro-3-methylbenzonitrile (2.90 g, 6.89 mmol) in THF (28 mL) was added TBAF (8.27 mL, 1 M solution in THF) over 1 minute. Upon complete addition, the reaction mixture was allowed to warm to 0° C. and concentrated under reduced pressure. The resulting orange residue was taken up in EtOAc (100 mL) and washed with H2O (400 mL). The biphasic mixture was separated and the aqueous layer extracted with EtOAc (2×50 mL). The combined organic layers were washed with brine (1×300 mL), dried (Na2SO4), filtered and concentrated under reduced pressure to provide a yellow/orange oil, which was purified by flash chromatography over silica gel (50% EtOAc in hexanes) to provide the title compound as a yellow solid (2.0 g, 95%): mp: 181-183° C.; 1H NMR (400 MHz, DMSO-d6, δ in ppm) 7.48 (d, J=8.0 Hz, 1H), 6.80 (d, J=8.0 Hz, 1H), 5.75 (d, J=8.8 Hz, 1H), 4.92 (dd, J=6.0, 8.8 Hz, 1H), 4.42 (m, 1H), 2.44 (s, 3H), 2.33 (s, 3H), 1.33 (d, J=6.4 Hz).

Workup

  1. additionUpon complete addition
  2. concentrationconcentrated under reduced pressure
  3. washwashed with H2O (400 mL)
  4. customThe biphasic mixture was separated
  5. extractionthe aqueous layer extracted with EtOAc (2×50 mL)
  6. washThe combined organic layers were washed with brine (1×300 mL)
  7. dry with materialdried (Na2SO4)
  8. filtrationfiltered
  9. concentrationconcentrated under reduced pressure
  10. customto provide a yellow/orange oil, which
  11. customwas purified by flash chromatography over silica gel (50% EtOAc in hexanes)

Sources & evidence

ORD record
ord-d229598fc201463d821918c00a8e0173
Source dataset
uspto-grants-2011_11
Patent number
US08067448B2

Reaction notes

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