Trifluoroacetic acid → (3aR,6aR)-Hexahydro-pyrrolo[3,4-b]pyrrole-5-carboxylic acid benzyl ester

HRID 12945Notes

Reaction equation

HRID 12945 reaction equation
C(OC([N:8]1[CH2:12][CH2:11][C@@H:10]2[CH2:13][N:14]([C:16]([O:18][CH2:19][C:20]3[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=3)=[O:17])[CH2:15][C@H:9]12)=O)(C)(C)C.FC(F)(F)C(O)=O>ClCCl>[CH2:19]([O:18][C:16]([N:14]1[CH2:13][C@@H:10]2[C@@H:9]([NH:8][CH2:12][CH2:11]2)[CH2:15]1)=[O:17])[C:20]1[CH:21]=[CH:22][CH:23]=[CH:24][CH:25]=1

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 44221919(3aR,6aR)-Hexahydro-pyrrolo[3,4-b]pyrrole-1,5-dicarboxylic acid 5-benzyl ester 1-tert-butyl ester

Product 1

HCID 44221501(3aR,6aR)-Hexahydro-pyrrolo[3,4-b]pyrrole-5-carboxylic acid benzyl ester

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

The product of Example 1A ((3aR,6aR)-hexahydro-pyrrolo[3,4-b]pyrrole-1,5-dicarboxylic acid 5-benzyl ester 1-tert-butyl ester) (4.5 g, 12.5 mmole), was stirred with a mixture of dichloromethane and trifluoroacetic acid (15 ml/15 ml) for 2 hours. The solvent was removed under reduced pressure, and the residue was basified with saturated sodium bicarbonate, then extracted with dichloromethane (3×). The combined organic layers were washed with brine, dried over sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by column chromatography (0.6% ammonium hydroxide and 6% methanol in dichloromethane) to provide the title compound. 1H NMR (CDCl3) δ ppm 7.28-7.40 (m, 5H) 5.12 (s, 2H) 3.74-3.87 (m, 1H) 3.53-3.71 (m, 2H) 3.36-3.48 (m, 1H) 3.18-3.32 (m, 1H) 3.01-3.13 (m, 1H) 2.88-3.01 (m, 1H) 2.70-2.83 (m, 1H) 1.87-2.03 (m, 1H) 1.58-1.76 (m, 1H). MS, (M+H)+=247.

Workup

  1. customThe solvent was removed under reduced pressure
  2. extractionextracted with dichloromethane (3×)
  3. washThe combined organic layers were washed with brine
  4. dry with materialdried over sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. customThe residue was purified by column chromatography (0.6% ammonium hydroxide and 6% methanol in dichloromethane)

Sources & evidence

ORD record
ord-1a5a0eefe63d42aa8fe959c1e4937d77
Source dataset
uspto-grants-2010_06
Patent number
US07728031B2

Reaction notes

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