Tetrabutylammonium Fluoride → HCID 44200173, compound

HRID 2388556Notes

Reaction equation

HRID 2388556 reaction equation
[Si]([O:8][CH2:9][CH2:10][C@@H:11]([NH:25][C:26]1[CH:33]=[CH:32][C:29]([C:30]#[N:31])=[C:28]([Cl:34])[C:27]=1[CH3:35])[C:12]1[O:13][C:14]([C:17]2[CH:22]=[CH:21][C:20]([C:23]#[N:24])=[CH:19][CH:18]=2)=[N:15][N:16]=1)(C(C)(C)C)(C)C.[F-].C([N+](CCCC)(CCCC)CCCC)CCC>C1COCC1.CCOC(C)=O>[Cl:34][C:28]1[C:27]([CH3:35])=[C:26]([NH:25][C@@H:11]([C:12]2[O:13][C:14]([C:17]3[CH:18]=[CH:19][C:20]([C:23]#[N:24])=[CH:21][CH:22]=3)=[N:15][N:16]=2)[CH2:10][CH2:9][OH:8])[CH:33]=[CH:32][C:29]=1[C:30]#[N:31]

Participants

5

Reactant 2

HCID 2724141Tetrabutylammonium FluorideHCID 67006515HCID 67006515, compound

Product 1

HCID 44200173HCID 44200173, compoundYield 87%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent2×HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
-40 °C

Procedure

To a 25 mL round bottom flask equipped with a magnetic stirrer and a septum was added (R)-4-(3-(tert-butyldimethylsilyloxy)-1-(5-(4-cyanophenyl)-1,3,4-oxadiazol-2-yl)propylamino)-2-chloro-3-methylbenzonitrile (900 mg, 177 mmol), which was then dissolved in anhydrous THF (50 mL) under an atmosphere of nitrogen and cooled to −40° C. To this was added the tetrabutylammonium fluoride as a 1M solution in THF (2.13 mL, 2.13 mmol) producing an instant color change to yellow. The mixture was then allowed to warm to −20° C. over a period of 2 h, at which point TLC analysis suggested the reaction was complete. The solvent was then removed under reduced pressure to yield a dark brown residue. This residue was taken up in EtOAc (40 mL) and washed with water (2×25 mL), brine (1×25 mL) and dried over Na2SO4. The solution was then filtered and concentrated under reduced pressure using rotary evaporation to reveal a yellow solid (1.08 g). Purification by flash column chromatography [EtOAc-hexanes (1:1) as eluent] afforded the title compound as a white crystalline solid (0.605 mg, 87%): 1H NMR (400 MHz, Acetone-d6, δ in ppm) 8.21 (d, J=9 Hz, 2H), 7.99 (d, J=9 Hz, 2H), 7.48 (d, J=9 Hz, 1H), 6.92 (d, J=9 Hz, 1H), 6.41 (d, J=9 Hz, 1H), 5.4 (m, 1H), 4.28-4.26 (m, 1H), 3.97-3.77 (m, 1H), 2.58-2.38 (m, 2H), 2.37.

Workup

  1. customTo a 25 mL round bottom flask equipped with a magnetic stirrer
  2. customproducing an instant color change to yellow
  3. temperatureto warm to −20° C. over a period of 2 h, at which point TLC analysis
  4. customThe solvent was then removed under reduced pressure
  5. customto yield a dark brown residue
  6. washwashed with water (2×25 mL), brine (1×25 mL)
  7. dry with materialdried over Na2SO4
  8. filtrationThe solution was then filtered
  9. concentrationconcentrated under reduced pressure
  10. customevaporation
  11. customPurification by flash column chromatography [EtOAc-hexanes (1:1) as eluent]

Sources & evidence

ORD record
ord-c192af83c5e64000b6e792f99b9e4db5
Source dataset
uspto-grants-2012_09
Patent number
US08268872B2

Reaction notes

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