反应 #312621

反应方程式

sodium bicarbonate

Triethylamine

2-Bromo-3,4,5-trifluorobenzaldehyde

cis-2,6-dimethylmorpholine

→

title compound

3-Bromo-6-(2,6-cis-dimethylmorpholin-4-yl)-4,5-difluorobenzaldehyde

溶剂

acetonitrile

acetonitrile

反应条件

后处理

1. 1
   温度The mixture was refluxed for 24 hours
2. 2
   其他The phases were separated
3. 3
   萃取the aqueous phase extracted twice with 500 ml ethyl acetate
4. 4
   洗涤The combined organic portions were washed twice with 500 ml brine
5. 5
   干燥dried over magnesium sulfate
6. 6
   过滤After filtering
7. 7
   其他rotary evaporation, 199.7 grams of oil
8. 8
   其他was recovered
9. 9
   workup.ADDITIONThe oil was diluted to ˜300 ml with heptane
10. 10
    其他placed in the freezer overnight
11. 11
    过滤The resulting yellow solid was filtered

实验过程

2-Bromo-3,4,5-trifluorobenzaldehyde (133.15 grams, 0.56 mol) was dissolved in 1000 ml dry acetonitrile. Triethylamine (118.65 ml, 0.85 mol) was added, followed by cis-2,6-dimethylmorpholine (Lancaster, 71.64 grams, 0.62 mol), and 125 ml additional acetonitrile. The mixture was refluxed for 24 hours, then cooled to room temperature, and poured into 1500 ml saturated sodium bicarbonate solution. The phases were separated and the aqueous phase extracted twice with 500 ml ethyl acetate. The combined organic portions were washed twice with 500 ml brine and then dried over magnesium sulfate. After filtering and rotary evaporation, 199.7 grams of oil was recovered. The oil was diluted to ˜300 ml with heptane to induce solidification and placed in the freezer overnight. The resulting yellow solid was filtered to yield 111.7 grams, 99.8% purity (HPLC) of title compound. Mp 88.1-92.0° C. HPLC analysis done on a Chromolith Performance column, RP-18e, 100-4.6 mm; Mobile phase: A=MeOH, B=0.1N TEAA (pH=7); Gradient: 60% A to 100% A over 5 minutes; wavelength: 254 nm; Retention time: 1.94 minutes.

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