反応 #46048

反応方程式

N-ethyldiisopropylamine

trifluoroacetic anhydride

(5S)-2-oxopyrrolidine-1,5-dicarboxylic acid

Dimethyaminopyridine

SuperHydride

→

4,5-dihydro-1H-pyrrole-1,5-dicarboxylic acid

収率 100.0%

溶媒

water

toluene

反応条件

後処理

1. 1
   その他did not exceed −45° C
2. 2
   workup.ADDITIONAfter complete addition
3. 3
   その他did not exceed −45° C
4. 4
   その他did not exceed −45° C
5. 5
   workup.ADDITIONAfter complete addition
6. 6
   温度the reaction mixture was warmed to 20 to 25° C. within one hour
7. 7
   workup.WAITkept for an additional 2 hours at this temperature
8. 8
   温度The reaction mixture was then cooled to 0° C.
9. 9
   その他did not exceed 5° C
10. 10
    その他Aqueous and organic phases were then separated
11. 11
    洗浄the organic phase was again washed with 48 liters of water (0 to 5° C.)
12. 12
    その他The organic later was then evaporated
13. 13
    その他degassed at 40° C

実験手順

The (5S)-2-oxopyrrolidine-1,5-dicarboxylic acid, 1-(1,1-dimethylethyl),5-ethyl ester (Formula G)(4.80 kg) was dissolved in toluene (30.97 liters; Kf max 0.01% water) and cooled to −50° C. This solution was charged with SuperHydride (LiEt3BH 1 M in THF; 19.96 liters) in a manner so that the reaction temperature did not exceed −45° C. After complete addition, the mixture was stirred at −45 to −50° C. for 30 minutes. N-ethyldiisopropylamine (DIPEA; 14.47 liters) was then added to the reaction mixture in a manner so that the temperature did not exceed −45° C. Dimethyaminopyridine (0.030 kg) was added as a solid to the mixture. The reaction mixture was then charged with trifluoroacetic anhydride (TFAA) (4.70 kg) in a manner so that the reaction temperature did not exceed −45° C. After complete addition, the reaction mixture was warmed to 20 to 25° C. within one hour and kept for an additional 2 hours at this temperature. The reaction mixture was then cooled to 0° C. and slowly charged with water (48.00 liters) so that the reaction temperature did not exceed 5° C. Aqueous and organic phases were then separated and the organic phase was again washed with 48 liters of water (0 to 5° C.). The organic later was then evaporated and degassed at 40° C. A yellowish oil was obtained with a yield of 4.5 kg (18.66 mol, 100%) of the 4,5-dihydro-1H-pyrrole-1,5-dicarboxylic acid, 1-(1-dimethylethyl), 5-ethyl ester (BOC-DHPEE)(Formula G′).

出典