Tetrabutylammonium Fluoride → 2-chloro-4-((1R,2S)-2-hydroxy-1-(5-(4-iodophenyl)-1,3,4-oxadiazol-2-yl)propylamino)-3-methylbenzonitrile

HRID 470846Notes

Reaction equation

HRID 470846 reaction equation
[Si]([O:8][C@@H:9]([CH3:34])[C@@H:10]([NH:23][C:24]1[CH:31]=[CH:30][C:27]([C:28]#[N:29])=[C:26]([Cl:32])[C:25]=1[CH3:33])[C:11]1[O:12][C:13]([C:16]2[CH:21]=[CH:20][C:19]([I:22])=[CH:18][CH:17]=2)=[N:14][N:15]=1)(C(C)(C)C)(C)C.CCCC[N+](CCCC)(CCCC)CCCC.[F-]>C1COCC1>[Cl:32][C:26]1[C:25]([CH3:33])=[C:24]([NH:23][C@@H:10]([C:11]2[O:12][C:13]([C:16]3[CH:17]=[CH:18][C:19]([I:22])=[CH:20][CH:21]=3)=[N:14][N:15]=2)[C@@H:9]([OH:8])[CH3:34])[CH:31]=[CH:30][C:27]=1[C:28]#[N:29]

Participants

4

Reactant 2

HCID 2724141Tetrabutylammonium FluorideHCID 670064554-((1R,2S)-2-(tert-Butyldimethylsilyloxy)-1-(5-(4-iodophenyl)-1,3,4-oxadiazol-2-yl)propylamino)-2-chloro-3-methylbenzonitrile

Product 1

HCID 670061822-chloro-4-((1R,2S)-2-hydroxy-1-(5-(4-iodophenyl)-1,3,4-oxadiazol-2-yl)propylamino)-3-methylbenzonitrileYield 94.3%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-30 °C

Procedure

To a solution of 4-((1R,2S)-2-(tert-butyldimethylsilyloxy)-1-(5-(4-iodophenyl)-1,3,4-oxadiazol-2-yl)propylamino)-2-chloro-3-methylbenzonitrile (2.0 g, 3.3 mmol) in THF (60 mL) was added TBAF (3.7 mL, 3.7 mmol, 1 M solution in THF) at −50° C. After addition, the reaction mixture was allowed to warm to −30° C. gradually (about 1 h), then quenched by adding saturated aqueous NH4Cl solution (20 mL) and extracted with EtOAc. The EtOAc extracts were washed with water, brine, dried over Na2SO4. Concentration provided a residue, which was purified by flash chromatography over silica gel to provide the title compound 2-chloro-4-((1R,2S)-2-hydroxy-1-(5-(4-iodophenyl)-1,3,4-oxadiazol-2-yl)propylamino)-3-methylbenzonitrile (1.54 g, 94%). 1H NMR (400 MHz, CDCl3, δ in ppm) 7.83 (d, J=8.6 Hz, 2H), 7.64 (d, J=8.6 Hz, 2H), 7.40 (d, J=8.6 Hz, 1H), 6.63 (d, J=8.6 Hz, 1H), 5.24 (d, J=8.6 Hz, 1H), 4.72 (dd, J=2.6, 8.6 Hz, 1H), 4.62 (m, 1H), 3.07 (d, J=4.1 Hz, 1H), 2.35 (s, 3H), 1.42 (d, J=6.5 Hz, 3H).

Workup

  1. additionAfter addition
  2. customquenched
  3. additionby adding saturated aqueous NH4Cl solution (20 mL)
  4. extractionextracted with EtOAc
  5. washThe EtOAc extracts were washed with water, brine
  6. dry with materialdried over Na2SO4
  7. concentrationConcentration
  8. customprovided a residue, which
  9. customwas purified by flash chromatography over silica gel

Sources & evidence

ORD record
ord-6f4fdb8b1e0b42ccafe33e1487b34281
Source dataset
uspto-grants-2014_01
Patent number
US08629167B2

Reaction notes

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