Réaction #46048

Équation de réaction

N-ethyldiisopropylamine

trifluoroacetic anhydride

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

Dimethyaminopyridine

SuperHydride

→

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

Rendement 100.0%

Solvants

water

toluene

Conditions de réaction

Traitement

1. 1
   Autredid not exceed −45° C
2. 2
   workup.ADDITIONAfter complete addition
3. 3
   Autredid not exceed −45° C
4. 4
   Autredid not exceed −45° C
5. 5
   workup.ADDITIONAfter complete addition
6. 6
   Températurethe 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
   TempératureThe reaction mixture was then cooled to 0° C.
9. 9
   Autredid not exceed 5° C
10. 10
    AutreAqueous and organic phases were then separated
11. 11
    Lavagethe organic phase was again washed with 48 liters of water (0 to 5° C.)
12. 12
    AutreThe organic later was then evaporated
13. 13
    Autredegassed at 40° C

Mode opératoire

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′).

Source