Tetrabutylammonium Fluoride → HCID 135870898, compound

HRID 2388435Notes

Reaction equation

HRID 2388435 reaction equation
[Si]([O:8][C@H:9]([CH3:35])[C@@H:10]([NH:24][C:25]1[CH:32]=[CH:31][C:28]([C:29]#[N:30])=[C:27]([Cl:33])[C:26]=1[CH3:34])[C:11]1[O:12][C:13]([C:16]2[CH:21]=[CH:20][C:19]([OH:22])=[C:18]([Cl:23])[CH:17]=2)=[N:14][N:15]=1)(C(C)(C)C)(C)C.CCCC[N+](CCCC)(CCCC)CCCC.[F-]>C1COCC1>[Cl:33][C:27]1[C:26]([CH3:34])=[C:25]([NH:24][C@@H:10]([C:11]2[O:12][C:13]([C:16]3[CH:21]=[CH:20][C:19]([OH:22])=[C:18]([Cl:23])[CH:17]=3)=[N:14][N:15]=2)[C@H:9]([OH:8])[CH3:35])[CH:32]=[CH:31][C:28]=1[C:29]#[N:30]

Participants

4

Reactant 2

HCID 2724141Tetrabutylammonium FluorideHCID 136343397HCID 136343397, compound

Product 1

HCID 135870898HCID 135870898, compoundYield 63.3%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-78 °C

Procedure

To a 100 mL round bottom flask was added 4-((1R,2R)-2-(tert-butyldimethylsilyloxy)-1-(5-(3-chloro-4-hydroxyphenyl)-1,3,4-oxadiazol-2-yl)propylamino)-2-chloro-3-methyl benzonitrile (586 mg, 0.9 mmol, 1.0 equiv.) and 60 mL of anhydrous THF. The solution was cooled to −78° C. and TBAF (1 mL, 0.99 mmol, 1.1 equiv., 1M in THF) was added dropwise via a syringe. The solution was stirred for 3 h while the temperature was kept below −30° C. The reaction was quenched with 25 mL of saturated ammonium chloride and diluted with 25 mL of EtOAc. The layers were separated and the organic layer was washed with distilled water (1×25 mL) and brine (1×25 mL). The organic layer was dried over Na2SO4 and was concentrated in vacuo to yield an off-white solid. The product was purified via automated flash chromatography (0→50% EtOAc/hexanes→100% EtOAc, 24 g of silica gel; TLC Rf=0.43, 100% EtOAc, vanillin stain) to provide the desired product as a white solid (239 mg, 63% yield). Other data: 1H NMR (400 MHz, acetone-d6, δ in ppm) 7.92 (d, J=2.15 Hz, 1H), 7.80 (dd, J=2.15, 8.6 Hz, 1H), 7.49 (d, J=8.6 Hz, 1H), 7.17 (d, J=8.6 Hz, 1H), 6.89 (d, J=8.79 Hz, 1H), 5.87 (d, J=8.79 Hz, 1H), 5.02 (dd, J=5.66, 8.79 Hz, 1H), 4.51 (m, 1H), 2.36 (s, 3H), 1.41 (d, J=6.45 Hz, 3H); LRMS (ESI+) exact mass calcd for C19H16Cl2N4O3 [M]+419.26, found 419.2.

Workup

  1. customwas kept below −30° C
  2. customThe reaction was quenched with 25 mL of saturated ammonium chloride
  3. additiondiluted with 25 mL of EtOAc
  4. customThe layers were separated
  5. washthe organic layer was washed with distilled water (1×25 mL) and brine (1×25 mL)
  6. dry with materialThe organic layer was dried over Na2SO4
  7. concentrationwas concentrated in vacuo
  8. customto yield an off-white solid
  9. customThe product was purified

Sources & evidence

ORD record
ord-2705fd9c8ba9461fbde1615e418b5e9e
Source dataset
uspto-grants-2012_09
Patent number
US08268872B2

Reaction notes

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