Tetrabutylammonium Fluoride → HCID 67006566, compound

HRID 2388511Notes

Reaction equation

HRID 2388511 reaction equation
[Si]([O:8][C@H:9]([CH3:39])[C@@H:10]([NH:26][C:27]1[CH:34]=[CH:33][C:30]([C:31]#[N:32])=[C:29]([C:35]([F:38])([F:37])[F:36])[CH:28]=1)[C:11]1[O:12][C:13]([C:16]2[CH:21]=[CH:20][C:19]([S:22]([CH3:25])(=[O:24])=[O:23])=[CH:18][CH:17]=2)=[N:14][N:15]=1)(C(C)(C)C)(C)C.CCCC[N+](CCCC)(CCCC)CCCC.[F-]>C1COCC1>[OH:8][C@H:9]([CH3:39])[C@@H:10]([NH:26][C:27]1[CH:34]=[CH:33][C:30]([C:31]#[N:32])=[C:29]([C:35]([F:36])([F:37])[F:38])[CH:28]=1)[C:11]1[O:12][C:13]([C:16]2[CH:17]=[CH:18][C:19]([S:22]([CH3:25])(=[O:24])=[O:23])=[CH:20][CH:21]=2)=[N:14][N:15]=1

Participants

4

Reactant 2

HCID 2724141Tetrabutylammonium FluorideHCID 67006231HCID 67006231, compound

Product 1

HCID 67006566HCID 67006566, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a pre-cooled (−70° C.) solution of 4-((1R,2R)-2-(tert-butyldimethylsilyloxy)-1-(5-(4-(methylsulfonyl)phenyl)-1,3,4-oxadiazol-2-yl)propylamino)-2-(trifluoromethyl)benzonitrile (1 g, 1.83 mmol) in THF (200 mL) was added TBAF (1.83 mL, 1.83 mmol, 1 M solution in THF) dropwise over 10 minutes. Upon complete addition the reaction mixture was concentrated under reduced pressure. The resulting residue was taken up in EtOAc (100 mL) and washed with H2O (80 mL). The biphasic mixture was separated and the aqueous layer extracted with EtOAc (2×100 mL). The combined organic layers were washed with brine (1×70 mL), dried (Na2SO4), filtered and concentrated under reduced pressure to provide a yellow oil, which was purified by flash chromatography over silica gel (50% EtOAc in hexanes then 100% EtOAc) to provide the title compound as an off-white solid. The resulting solid was diluted with CH2Cl2 (90 mL) and hexanes (70 mL) was added. Upon concentration of the suspension a white solid was provided (329 mg, 39%). 1H NMR (400 MHz, acetone-d6, δ in ppm) 8.24 (d, J=8.8 Hz, 2H), 8.16 (d, J=9 Hz, 2H), 7.74 (d, J=9 Hz, 1H), 7.38 (s, 1H), 7.19 (d, J=9 Hz, 1H), 7.01 (d, J=8 Hz, 1H), 5.19 (dd, J=6, 8 Hz, 1H), 4.59 (d, J=6 Hz, 1H), 4.49-4.42 (m, 1H), 3.2 (s, 3H) and 1.42 (d, J=7 Hz, 3H).

Workup

  1. additionUpon complete addition the reaction mixture
  2. concentrationwas concentrated under reduced pressure
  3. washwashed with H2O (80 mL)
  4. customThe biphasic mixture was separated
  5. extractionthe aqueous layer extracted with EtOAc (2×100 mL)
  6. washThe combined organic layers were washed with brine (1×70 mL)
  7. dry with materialdried (Na2SO4)
  8. filtrationfiltered
  9. concentrationconcentrated under reduced pressure
  10. customto provide a yellow oil, which
  11. customwas purified by flash chromatography over silica gel (50% EtOAc in hexanes

Sources & evidence

ORD record
ord-0a0663c68a9041ec8fd555c36386ab1c
Source dataset
uspto-grants-2012_09
Patent number
US08268872B2

Reaction notes

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