반응 #1869166

반응 방정식

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

Water

sodium borohydride

→

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

수율 98.0%

용매

tetrahydrofuran

1,4-dioxane

반응 조건

후처리

1. 1
   workup.STIRRINGthe resulting solution stirred for 45 minutes at room temperature
2. 2
   기타When all the 2-chloro-1-[6-(2,5-dimethylpyrrol-1-yl)pyridin-3-yl]ethanone was consumed the reaction mixture
3. 3
   온도was cooled to 19° C.
4. 4
   workup.ADDITIONtreated with concentrated HCl (36% w/w) (1.08 L) over 40 minutes
5. 5
   온도The mixture was cooled to 11° C.
6. 6
   workup.ADDITIONNaOH (32% w/w) (1.64 L) was added over 45 minutes
7. 7
   온도maintaining the temperature below 25° C
8. 8
   기타When 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
    기타to separate
12. 12
    추출The aqueous phase was extracted with DCM (2.50 L)
13. 13
    세척the combined organic phases were washed with water (2×1.0 L)
14. 14
    농축concentrated in vacuo

실험 절차

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+).

출처