反応 #5217

反応方程式

iodine

6-chloro-2-methoxy-3-pyridinecarboxaldehyde

n-BuLi

N,N,N'-trimethylethylenediamine

n-BuLi

→

6-Chloro-4-iodo-2-methoxy-3-pyridinecarboxaldehyde

収率 51.3%

溶媒

1,2-dimethoxyethane

1,2-dimethoxyethane

—

hexanes

1,2-dimethoxyethane

反応条件

後処理

1. 1
   その他at -23° C
2. 2
   workup.STIRRINGAfter stirring for 15 min
3. 3
   workup.STIRRINGthe dark mixture was stirred an additional 2 h at -23° C
4. 4
   その他at -78° C
5. 5
   workup.STIRRINGAfter stirring at -78° C. for 30 min
6. 6
   その他the cooling bath was removed
7. 7
   温度to warm for 20 min
8. 8
   その他quenched with water
9. 9
   抽出The mixture was extracted with ether (2×30 mL)
10. 10
    洗浄the combined organic layers were washed successively with 30-mL portions of 10% aqueous Na2S2O3, water and brine
11. 11
    乾燥dried over MgSO4
12. 12
    濃縮Concentration
13. 13
    その他afforded 4.62 g (89%) of crude product to which
14. 14
    workup.STIRRINGThe mixture was stirred
15. 15
    workup.WAITto stand at 5° C. overnight
16. 16
    ろ過Filtration

実験手順

To a solution of N,N,N'-trimethylethylenediamine (2.46 mL, 19.23 mmol) in 15 mL of 1,2-dimethoxyethane at -23° C. was added n-BuLi (9.22 mL, 19.23 mmol), and the solution was stirred at -23° C. for 20 min. The mixture was transferred using a double-tipped needle to a solution of 6-chloro-2-methoxy-3-pyridinecarboxaldehyde (3.0 g, 17.5 mmol) in 40 mL of 1,2-dimethoxyethane at -23° C. After stirring for 15 min, n-BuLi (12.6 mL, 26.2 mmol) was added and the dark mixture was stirred an additional 2 h at -23° C. The solution was transferred using a double-tipped needle to a solution of iodine (8.04 g, 31.7 mmol) in 40 mL of 1,2-dimethoxyethane at -78° C. After stirring at -78° C. for 30 min, the cooling bath was removed and the reaction mixture was allowed to warm for 20 min, then quenched with water. The mixture was extracted with ether (2×30 mL) and the combined organic layers were washed successively with 30-mL portions of 10% aqueous Na2S2O3, water and brine, and dried over MgSO4. Concentration afforded 4.62 g (89%) of crude product to which was added 50 mL of hexanes. The mixture was stirred and allowed to stand at 5° C. overnight. Filtration gave 2.67 g of 6-Chloro-4-iodo-2-methoxy-3-pyridinecarboxaldehyde as a yellow solid: mp 120°-124° C. Concentration of the hexane washings and purification of the residue by radial preparative thin-layer chromatography (silica gel, 5% ethyl acetate/hexanes) gave an additional 1.41 g of product (mp 120°-124° C.), raising the total yield of the compound to 78%. Recrystallization from hexanes gave an analytical sample as a bright yellow solid: mp 129°-130° C. 1H NMR (300 MHz, CDCl3) δ 10.16 (s, 1H), 7.59 (s, 1H), 4.07 (s, 1H); IR (nujol) 1690, 1350, 1260, 1095, 1010, 900, 840 cm-1.

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