تفاعل #84301

معادلة التفاعل

2-bromo-3,5-dichloropyridine

(S)—N-methoxy-N-methyl-2-(tert-butoxycarbonylamino)propionamide

ammonium chloride

water

→

desired product

المردود 65.5%

tert-butyl (S)—N-[2-(3,5-dichloropyridin-2-yl)-1-methyl-2-oxoethyl]carbamate

المردود 65.5%

المذيبات

tetrahydrofuran

tetrahydrofuran

tetrahydrofuran

ظروف التفاعل

المعالجة

1. 1
   workup.ADDITIONafter the addition
2. 2
   workup.STIRRINGthe mixture was stirred at the same temperature for 15 minutes
3. 3
   workup.ADDITIONafter the addition
4. 4
   workup.STIRRINGthe mixture was stirred at the same temperature for another 2 hours
5. 5
   أخرىAfter completion of the reaction
6. 6
   استخلاصextracted with ethyl acetate (40 ml×2)
7. 7
   غسيلwashed with water (40 ml×1)
8. 8
   تجفيفdried over saturated aqueous sodium chloride
9. 9
   أخرىanhydrous sodium sulfate, and the solvent was evaporated under reduced pressure
10. 10
    أخرىThe resulting residue was purified by silica gel column chromatography

الإجراء التجريبي

To 11.0 g of 2-bromo-3,5-dichloropyridine in 5 ml of tetrahydrofuran, 36.4 ml of a 1.3 M tetrahydrofuran solution of isopropylmagnesium chloride-lithium chloride complex was added dropwise with stirring at −20° C., and after the addition, the mixture was stirred at the same temperature for 15 minutes. Then, to the reaction mixture, 5.0 g of (S)—N-methoxy-N-methyl-2-(tert-butoxycarbonylamino)propionamide in 36 ml of tetrahydrofuran was added dropwise, and after the addition, the mixture was stirred at the same temperature for another 2 hours. After completion of the reaction, the reaction mixture was mixed with 30 ml of saturated aqueous ammonium chloride and 10 ml of water and extracted with ethyl acetate (40 ml×2), the resulting organic layers were combined, washed with water (40 ml×1) and dried over saturated aqueous sodium chloride and then anhydrous sodium sulfate, and the solvent was evaporated under reduced pressure. The resulting residue was purified by silica gel column chromatography using ethyl acetate-hexane (with a gradient of from 10:0 to 3:7) to obtain 4.5 g of the desired product as a pale yellow oil.

المصدر