Trifluoroacetic anhydride → 4,5-dihydro-1H-pyrrole-1,5-dicarboxylic acid

HRID 17770Notes

Reaction equation

HRID 17770 reaction equation
O=[C:2]1[CH2:6][CH2:5][C@@H:4]([C:7]([OH:9])=[O:8])[N:3]1[C:10]([OH:12])=[O:11].[Li+].[B-](CC)(CC)CC.C(N(C(C)C)C(C)C)C.CN(C1C=CC=CN=1)C.FC(F)(F)C(OC(=O)C(F)(F)F)=O>C1(C)C=CC=CC=1.O>[N:3]1([C:10]([OH:12])=[O:11])[CH:4]([C:7]([OH:9])=[O:8])[CH2:5][CH:6]=[CH:2]1

Participants

8

Reactant 5

HCID 9845Trifluoroacetic anhydrideHCID 218852-DimethylaminopyridineHCID 81531DiisopropylethylamineHCID 20759491(s)-5-Oxopyrrolidine-1,2-dicarboxylic acidHCID 23712863Lithium triethylborohydride

Product 1

HCID 211030884,5-dihydro-1H-pyrrole-1,5-dicarboxylic acidYield 100%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 1140TolueneSolvent

Conditions

Temperature
-50 °C

Procedure

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′).

Workup

  1. customdid not exceed −45° C
  2. additionAfter complete addition
  3. customdid not exceed −45° C
  4. customdid not exceed −45° C
  5. additionAfter complete addition
  6. temperaturethe reaction mixture was warmed to 20 to 25° C. within one hour
  7. waitkept for an additional 2 hours at this temperature
  8. temperatureThe reaction mixture was then cooled to 0° C.
  9. customdid not exceed 5° C
  10. customAqueous and organic phases were then separated
  11. washthe organic phase was again washed with 48 liters of water (0 to 5° C.)
  12. customThe organic later was then evaporated
  13. customdegassed at 40° C

Sources & evidence

ORD record
ord-bd49ee621976495b824e11a27ee0d893
Source dataset
uspto-grants-2010_06
Patent number
US07741082B2

Reaction notes

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