Phosphate → HCID 71517830, compound

HRID 1775499Notes

Reaction equation

HRID 1775499 reaction equation
[CH2:1]([O:3][C:4](=[O:25])[C:5]([CH2:12][CH2:13][N:14]1[C:22](=[O:23])[C:21]2[C:16](=[CH:17][CH:18]=[CH:19][CH:20]=2)[C:15]1=[O:24])([CH3:11])[C:6]([O:8]CC)=[O:7])[CH3:2].P([O-])([O-])([O-])=O.[OH-].[Na+]>C(O)C>[O:24]=[C:15]1[C:16]2[C:21](=[CH:20][CH:19]=[CH:18][CH:17]=2)[C:22](=[O:23])[N:14]1[CH2:13][CH2:12][C@:5]([C:4]([O:3][CH2:1][CH3:2])=[O:25])([CH3:11])[C:6]([OH:8])=[O:7]

Participants

5

Reactant 3

HCID 1061PhosphateHCID 14798Sodium Hydroxide2×HCID 71517829HCID 71517829, compound

Product 1

HCID 71517830HCID 71517830, compoundYield 72%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

In a 1 L round bottom flask, diethyl[2-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)ethyl](methyl)propanedioate (Banerjee, S.; Wiggins, W. J.; Geoghegan, J. L.; Anthony, C. T.; Woltering, E. A.; Masterson, D. S. Org. Biomol. Chem., 2013, 11, 6307-6319) (9.56 g, 27.5 mmol) was suspended into a 0.1 M phosphate buffer at pH 7.4 (784 mL) and ethanol (16 mL). Pig liver esterase (0.90 mL, technical grade, 2.8 kilounits/mL) was then added and the reaction was stirred rapidly at room temperature for 17 h. The mixture was sonicated, additional pig liver esterase was added (0.1 mL) and the pH was adjusted to −7-8 with 1.0 M aqueous NaOH and stirring was continued for 7 h. Additional pig liver esterase (0.05 mL) was added, the pH was adjusted to −7-8 with 1.0 M aqueous NaOH and stirring was continued for 16 h. The mixture was transferred to a separatory funnel and extracted with tert-butylmethylether (2×300 mL). The aqueous phase was acidified to pH 1 with concentrated HCl and extracted with tert-butylmethylether (3×300 mL) and EtOAc (3×300 mL). The combined organic phases were dried over MgSO4, filtered, washed with brine, dried again over MgSO4, filtered and concentrated. The crude product was purified via silica gel chromatography eluting with 15-50% EtOAc/heptanes to give the title compound (6.29 g, 72%) as a white solid whose spectroscopic properties were identical to previous reports.

Workup

  1. additionPig liver esterase (0.90 mL, technical grade, 2.8 kilounits/mL) was then added
  2. customThe mixture was sonicated
  3. additionadditional pig liver esterase was added (0.1 mL)
  4. stirringstirring
  5. waitwas continued for 7 h
  6. additionAdditional pig liver esterase (0.05 mL) was added
  7. stirringstirring
  8. waitwas continued for 16 h
  9. customThe mixture was transferred to a separatory funnel
  10. extractionextracted with tert-butylmethylether (2×300 mL)
  11. extractionextracted with tert-butylmethylether (3×300 mL) and EtOAc (3×300 mL)
  12. dry with materialThe combined organic phases were dried over MgSO4
  13. filtrationfiltered
  14. washwashed with brine
  15. dry with materialdried again over MgSO4
  16. filtrationfiltered
  17. concentrationconcentrated
  18. customThe crude product was purified via silica gel chromatography
  19. washeluting with 15-50% EtOAc/heptanes

Sources & evidence

ORD record
ord-5554f536f33b498a95f33419928ae37c
Source dataset
uspto-grants-2016_02
Patent number
US09260439B2

Reaction notes

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