反応 #1869166

反応方程式

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

Water

sodium borohydride

→

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

収率 98.0%

溶媒

tetrahydrofuran

1,4-dioxane

反応条件

後処理

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

実験手順

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+).

出典