Sodium Hydroxide → HCID 71695763, compound

HRID 2037293Notes

Reaction equation

HRID 2037293 reaction equation
[OH-].[Na+].C([NH:6][C@@:7]1([C:20]([O:22]CC)=[O:21])[CH2:14][C:11]2([CH2:13][CH2:12]2)[C@@H:10]2[C@H:8]1[C@H:9]2[C:15]([O:17]CC)=[O:16])(=O)C>>[NH2:6][C@@:7]1([C:20]([OH:22])=[O:21])[CH2:14][C:11]2([CH2:13][CH2:12]2)[C@@H:10]2[C@H:8]1[C@H:9]2[C:15]([OH:17])=[O:16]

Participants

3

Reactant 2

HCID 14798Sodium Hydroxide2×HCID 86691268HCID 86691268, compound

Product 1

HCID 71695763HCID 71695763, compoundYield 100%

Procedure

Add 2M sodium hydroxide (11.5 mL, 23.1 mmol) with diethyl (1S,2S,5R,6S)-2-acetamidospiro[bicyclo[3.1.0]hexane-4,1′-cyclopropane]-2,6-dicarboxylate (1.19 g, 3.8 mmol). Upon addition heat the reaction mixture to reflux under a blanket of nitrogen. After 21 hours add excess 2M sodium hydroxide (5.8 mL, 11.5 mmol) and resume heating for 120 hours. Purify by cation exchange chromatography (Dowex™ 50X8-100) as follows. Filter any insoluble particles and rinse with HPLC grade water. Concentrate the solution by half. Load the solution onto the resin, allowing to flow through the column at a drip rate of about 1 drop every 1-2 seconds. After the initial loading volume has dropped to the resin surface, rinse the resin with HPLC grade water (˜1 to 2 column volumes) and repeat 3 times. Monitor the pH of the effluent and pursue rinsing with HPLC grade water until application complete (return of pH back to pH=7.). Once the complete pH cycle has been observed and the effluent has returned to pH=7, wash the column with at least one column volume each of HPLC grade water, HPLC grade water: tetrahydrofuran (1:1), then HPLC grade water. Displace the product from the resin with 10% pyridine: HPLC grade water and continue elution with 10% pyridine: HPLC grade water until no additional product was detected by TLC. Combine the fractions containing the desired material, concentrate to dryness to give a white solid. Freeze-dry to yield the title compound (795 mg, 3.8 mmol). MS (m/z): 212 (M+1). 1H NMR (D2O+5% d5-pyridine) δ: 0.38 (m, 1H), 0.45 (m, 1H), 0.55 (m, 1H), 0.69 (m, 1H), 1.50 (dd, J=2.9 Hz, 1H), 1.62 (d, J=13.7 Hz, 1H), 1.78 (m, 2H), 2.11 (dd, J=2.9 Hz, 1H).

Workup

  1. additionUpon addition
  2. temperatureheat the reaction mixture
  3. temperatureto reflux under a blanket of nitrogen
  4. temperatureresume heating for 120 hours
  5. customPurify by cation exchange chromatography (Dowex™ 50X8-100)
  6. filtrationFilter any insoluble particles
  7. washrinse with HPLC grade water
  8. concentrationConcentrate the solution by half
  9. customto flow through the column at a drip rate of about 1 drop every 1-2 seconds
  10. additionAfter the initial loading volume has dropped to the resin surface
  11. washrinse the resin with HPLC grade water (˜1 to 2 column volumes) and repeat 3 times
  12. washMonitor the pH of the effluent and pursue rinsing with HPLC grade water until application complete (return of pH back to pH=7
  13. washwash the column with at least one column volume each of HPLC grade water, HPLC grade water: tetrahydrofuran (1:1)
  14. washelution with 10% pyridine
  15. additionCombine the fractions containing the desired material
  16. concentrationconcentrate to dryness
  17. customto give a white solid
  18. customFreeze-dry

Sources & evidence

ORD record
ord-b98ffb0bb1ba4d05b517872a5aa644c3
Source dataset
uspto-grants-2013_11
Patent number
US08575214B2

Reaction notes

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