Oxalic Acid → Oxalic acid--tert-butyl (1S,3aR,6aS)-octahydrocyclopenta[c]pyrrole-1-carboxylate (1/1)

HRID 1923440Notes

Reaction equation

HRID 1923440 reaction equation
[C:1]([O:5][C:6]([C@@H:8]1[C@H:12]2[CH2:13][CH2:14][CH2:15][C@H:11]2[CH2:10][NH:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[C:16]([OH:21])(=[O:20])[C:17]([OH:19])=[O:18].C([O-])(=O)C([O-])=O>C(OC(C)(C)C)(=O)C.CC(O)C>[C:16]([OH:21])(=[O:20])[C:17]([OH:19])=[O:18].[C:1]([O:5][C:6]([C@@H:8]1[C@H:12]2[CH2:13][CH2:14][CH2:15][C@H:11]2[CH2:10][NH:9]1)=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

6

Reactant 3

HCID 971Oxalic AcidHCID 71081OxalateHCID 59428239tert-Butyl (1S,3aR,6aS)-octahydrocyclopenta[c]pyrrole-1-carboxylate

Product 1

HCID 67080120Oxalic acid--tert-butyl (1S,3aR,6aS)-octahydrocyclopenta[c]pyrrole-1-carboxylate (1/1)Yield 84.6%

Reagents, catalysts & solvents 2

HCID 3776IsopropanolSolventHCID 10908tert-Butyl acetateSolvent

Conditions

Temperature
21 °C

Procedure

97.9 g (463.3 mmol) of (1S,3aR,6aS)-octahydrocyclopenta[c]pyrrole-1-carboxylic acid t-butyl ester from the two preparations according to Step 1 were dissolved in 750 mL t-butyl acetate and charged to a 3 L four-neck flask equipped with overhead mechanical stirring, a thermometer, addition funnel, and reflux condenser. With stirring at ambient temperature (˜21° C.), a solution of 44.0 g (488.6 mmol) of oxalic acid in 750 mL 2-propanol was added dropwise over 37 minutes, increasing the mixture's temperature to 31° C. Solids began to precipitate after addition of ˜50 mL of the oxalic acid solution, and resulted in a thick suspension after the addition of 450 mL. After addition of 500 mL of the oxalate solution, the precipitated solids redissolved to provide a dark yellow solution. Solids precipitated again rapidly after the addition of 600 mL of the oxalic solution and persisted through the end of the oxalic acid addition. This suspension was then heated 78° C. to provide a thin suspension which was allowed to cool passively with stirring to ambient temperature (˜21° C.). After 16 hours since the cooling began, the precipitated solids were collected by filtration and washed successively with isopropanol (450 mL), isopropyl acetate (450 mL), and methyl t-butyl methyl ether (450 mL). The solids were dried in a vacuum oven (30° C., 25″ vacuum, N2 stream) to provide 118.1 g (1S,3aR,6aS)-octahydrocyclopenta[c]pyrrole-1-carboxylic acid t-butyl ester oxalic acid 1:1 salt (64% yield from (1S,3aR,6aS)-octahydrocyclopenta[c]pyrrole-1-carboxylic acid hydrochloride) as a dense, tan free flowing powder (99.7% purity by GC analysis), which exhibited the expected 1H-NMR spectrum for (1S,3aR,6aS)-octahydrocyclopenta[c]pyrrole-1-carboxylic acid t-butyl ester oxalic acid (1:1) salt.

Workup

  1. additioncharged to a 3 L four-neck flask
  2. customequipped with overhead mechanical stirring
  3. additiona thermometer, addition funnel
  4. temperaturereflux condenser
  5. temperatureincreasing the mixture's temperature to 31° C
  6. customto precipitate
  7. additionafter addition of ˜50 mL of the oxalic acid solution
  8. customresulted in a thick suspension
  9. additionafter the addition of 450 mL
  10. dissolutionthe precipitated solids redissolved
  11. customto provide a dark yellow solution
  12. customSolids precipitated again rapidly
  13. additionafter the addition of 600 mL of the oxalic solution
  14. additionpersisted through the end of the oxalic acid addition
  15. temperatureThis suspension was then heated 78° C.
  16. customto provide a thin suspension which
  17. temperatureto cool passively
  18. stirringwith stirring to ambient temperature (˜21° C.)
  19. filtrationthe precipitated solids were collected by filtration
  20. washwashed successively with isopropanol (450 mL), isopropyl acetate (450 mL), and methyl t-butyl methyl ether (450 mL)
  21. dry with materialThe solids were dried in a vacuum oven (30° C., 25″ vacuum, N2 stream)

Sources & evidence

ORD record
ord-d87063c2b3d949d2b6bf8d68fc04de0f
Source dataset
uspto-grants-2012_05
Patent number
US08178333B2

Reaction notes

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