Reaktion #1869166

Reaktionsgleichung

2-chloro-1-[6-(2,5-dimethylpyrrol-1-yl)pyridin-3-yl]ethanone

Water

sodium borohydride

→

2-(2,5-Dimethylpyrrol-1-yl)-5-oxiranylpyridine

Ausbeute 98.0%

Lösungsmittel

tetrahydrofuran

1,4-dioxane

Reaktionsbedingungen

Aufarbeitung

1. 1
   workup.STIRRINGthe resulting solution stirred for 45 minutes at room temperature
2. 2
   SonstigeWhen all the 2-chloro-1-[6-(2,5-dimethylpyrrol-1-yl)pyridin-3-yl]ethanone was consumed the reaction mixture
3. 3
   Temperaturwas cooled to 19° C.
4. 4
   workup.ADDITIONtreated with concentrated HCl (36% w/w) (1.08 L) over 40 minutes
5. 5
   TemperaturThe mixture was cooled to 11° C.
6. 6
   workup.ADDITIONNaOH (32% w/w) (1.64 L) was added over 45 minutes
7. 7
   Temperaturmaintaining the temperature below 25° C
8. 8
   SonstigeWhen all the chloroalcohol intermediate was consumed
9. 9
   workup.ADDITIONDCM (5.0 L) and water (5.0 L) were added
10. 10
    workup.STIRRINGthe mixture was stirred
11. 11
    Sonstigeto separate
12. 12
    ExtraktionThe aqueous phase was extracted with DCM (2.50 L)
13. 13
    Waschenthe combined organic phases were washed with water (2×1.0 L)
14. 14
    Einengenconcentrated in vacuo

Vorschrift

Water (1.08 Kg) was added dropwise to a suspension of sodium borohydride (0.17 Kg, 4.36 mol) in 1,4-dioxane (6.49 L) at 16° C. and the resulting solution stirred at room temperature. A solution of 2-chloro-1-[6-(2,5-dimethylpyrrol-1-yl)pyridin-3-yl]ethanone (1.08 Kg, 4.35 mol) in tetrahydrofuran (2.16 L) was added over 1 hour and the resulting solution stirred for 45 minutes at room temperature. When all the 2-chloro-1-[6-(2,5-dimethylpyrrol-1-yl)pyridin-3-yl]ethanone was consumed the reaction mixture was cooled to 19° C. and treated with concentrated HCl (36% w/w) (1.08 L) over 40 minutes. The mixture was cooled to 11° C. and NaOH (32% w/w) (1.64 L) was added over 45 minutes maintaining the temperature below 25° C. The mixture was then allowed to granulate at room temperature overnight. When all the chloroalcohol intermediate was consumed, DCM (5.0 L) and water (5.0 L) were added and the mixture was stirred before allowing the phases to separate. The aqueous phase was extracted with DCM (2.50 L) and the combined organic phases were washed with water (2×1.0 L) and concentrated in vacuo. Yield 98% (0.92 Kg) δH (CDCl3, 300 MHz) 2.10 (6H, s), 2.90 (1H, dd), 3.25 (1H, dd), 4.00 (1H, dd), 5.90 (2H, s), 7.20 (1H, d), 7.70 (1H, dd), 8.40 (1H, d) ppm. MS m/z 215 (MH+).

Quelle