Hexane → 2,2-Difluoro-2-pyridin-2-ylethyl 4-methylbenzenesulfonate

HRID 45573

Reaktionsgleichung

Reaktionsgleichung von HRID 45573
[F:1][C:2]([F:11])([C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][N:6]=1)[CH2:3][OH:4].[CH3:12]S([O-])(=O)=O.[S:17](Cl)(Cl)(=[O:19])=[O:18].[CH3:22][CH2:23][CH2:24][CH2:25][CH2:26][CH3:27]>>[CH3:12][C:24]1[CH:23]=[CH:22][C:27]([S:17]([O:4][CH2:3][C:2]([F:1])([F:11])[C:5]2[CH:10]=[CH:9][CH:8]=[CH:7][N:6]=2)(=[O:19])=[O:18])=[CH:26][CH:25]=1

Komponenten

5

Edukt 4

HCID 8058HexaneHCID 24648Sulfuryl chlorideHCID 85257MethanesulfonateHCID 99422162,2-Difluoro-2-(pyridin-2-YL)ethanol

Produkt 1

HCID 582496422,2-Difluoro-2-pyridin-2-ylethyl 4-methylbenzenesulfonateAusbeute 76,2 %

Reaktionsbedingungen

Temperatur
5 °C

Versuchsvorschrift

2,2-Difluoro-2-pyridin-2-ylethanol (H) from step 2 (10 g) was dissolved in 100 mL of MDC, 19 g of TEA was added, then the RM was cooled to 0-10° C. To the cooled solution, 16.77 g of pTsCl was added over a period of 1 hour and stirred for 24 hours at RT. The RM was then quenched with 100 mL of 10% sodium bicarbonate solution and the organic layers were separated. The aqueous layer was extracted with (100 mL×3) MDC. The organic layer was combined and washed with 10% sodium bicarbonate (150 mL), followed by water (150 mL) and a brine solution (150 mL). The organic layer was distilled under vacuum. The crude mass obtained was treated with 30 mL of hexane with cooling and filtered, resulting in pure tosylate. (Weight=15 g, Yield=76.2%). It should be noted that the above process may be followed for the preparation of other sulfonates such as methanesulfonate by using the corresponding sulfonyl chloride (e.g. methanesulfonyl chloride). The compound thus prepared is used in the preparation of a compound of formula (K2). 1H-NMR (CDCl3, δ, ppm): 400 MHz: 2.45 (s, 3H), 4.63-4.69 (t, 2H), 7.31-7.33 (d, 2H), 7.36-7.39 (t, 1H), 7.63-7.65 (d, 1H), 7.71-7.73 (d, 2H), 7.79-7.82 (t, 1H), 8.55-8.54 (d, 1H); MS m/z: 314 (M+1).

Aufarbeitung

  1. additionwas added
  2. additionTo the cooled solution, 16.77 g of pTsCl was added over a period of 1 hour
  3. customThe RM was then quenched with 100 mL of 10% sodium bicarbonate solution
  4. customthe organic layers were separated
  5. extractionThe aqueous layer was extracted with (100 mL×3) MDC
  6. washwashed with 10% sodium bicarbonate (150 mL)
  7. distillationThe organic layer was distilled under vacuum
  8. customThe crude mass obtained
  9. temperaturewith cooling
  10. filtrationfiltered
  11. customresulting in pure tosylate
  12. customThe compound thus prepared
  13. customis used in the preparation of a compound of formula (K2)

Quellen und Nachweise

ORD-Eintrag
ord-8cb400154974416c930cc6404e1a201c
Quelldatensatz
uspto-grants-2013_09
Patentnummer
US08541580B2

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