Ethanol → HCID 58815868, compound

HRID 2245888Notes

Reaction equation

HRID 2245888 reaction equation
C(OC(=O)CC[CH2:7][CH2:8][NH:9][CH:10]1[CH2:15][CH2:14][N:13]([C:16](=O)[C:17]2[CH:22]=[CH:21][CH:20]=[C:19]([C@@H:23]([N:31]3[CH2:36][C@@H:35]([CH3:37])[N:34]([CH2:38][CH:39]=[CH2:40])[CH2:33][C@@H:32]3[CH3:41])[C:24]3[CH:29]=[CH:28][CH:27]=[C:26]([OH:30])[CH:25]=3)[CH:18]=2)[CH2:12][CH2:11]1)C.[CH2:44]([OH:46])[CH3:45].[OH-:47].[Na+].S(=O)(=O)(O)[OH:50]>O>[CH2:38]([N:34]1[C@H:35]([CH3:37])[CH2:36][N:31]([C@@H:23]([C:24]2[CH:29]=[CH:28][CH:27]=[C:26]([OH:30])[CH:25]=2)[C:19]2[CH:18]=[C:17]([CH:22]=[CH:21][CH:20]=2)[C:16]([N:13]2[CH2:14][CH2:15][CH:10]([NH:9][CH2:8][CH2:7][CH2:45][C:44]([OH:50])=[O:46])[CH2:11][CH2:12]2)=[O:47])[C@@H:32]([CH3:41])[CH2:33]1)[CH:39]=[CH2:40]

Participants

6

Reactant 4

HCID 702EthanolHCID 1118Sulfuric AcidHCID 14798Sodium HydroxideHCID 68695686HCID 68695686, compound

Product 1

HCID 58815868HCID 58815868, compound

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

The preceding ester, Example 141, was hydrolyzed as follows. A 50 mL round bottom flask equipped with a magnetic stir bar was charged with 0.70 g (1.2 mmol, 1 eq) of 4-[(1-{3-[(R)-((2S,5R)-4-allyl-2,5-dimethyl-1-piperazinyl)(3-hydroxyphenyl)-methyl]-benzoyl}-4-piperidinylamino)methyl]butyric acid ethyl ester, 5.0 mL ethanol, and 3.0 mL (6 mmol, 5 eq) of 2 N aqueous NaOH solution. The reaction was stirred at room temperature for 3 days and neutralized with 3.0 mL (6 mmol, 5 eq) of 2 N aqueous sulfuric acid. After stirring for 30 minutes, the reaction was filtered to remove the sodium sulfate, and the solvent was removed in vacuo. The residue was dissolved in 25 mL of dichloromethane and extracted with 2×10 mL of water. The aqueous phase was diluted with 50 mL ethanol and concentrated in vacuo, leaving an off-white solid. This material was dissolved in 8 mL of water, filtered through a 0.2 □m polypropylene membrane, and lyophilized to give 0.488 g of the title compound as a white solid. Calculated for C32H44N4O4 1.5 H2SO4 1.5 H2O 0.25 Na2SO4: %C, 50.68; H, 6.65; N, 7.39. Found: %C, 50.73; H, 6.65; N, 7.39. 1H NMR (300 MHz, D2O with ˜0.1 N NaOD): 7.37-7.18 (m, 3H), 7.10 (d, J=7.5 Hz, 1H), 6.92 (t, J=7.0 Hz, I H), 6.45-6.36 (m, 2H), 6.28 (t, J=7.0 Hz, 1H), 5.76-5.62 (m, 1H), 5.10-5.04 (m, 3H), 4.27 (br d, J=12.5 Hz, 1H), 3.46 (m, 1H), {tilde over (□)}□dd, J=5.3, 13.4 Hz, 1H), {tilde over (□)}1t, J=13 Hz, 1H), 2.79-2.61 (m, 5H), 2.46-2.31 (m, 4H), 2.05-1.98 (m, 3H), 1.96-1.85 (m, 2H), 1.69-1.50 (m, 3H), 1.16-0.92 (m, 2H), 0.95 (distorted t, 3H), 0.81 (d, J=5.8 Hz, 3H).

Workup

  1. customA 50 mL round bottom flask equipped with a magnetic stir bar
  2. stirringAfter stirring for 30 minutes
  3. filtrationthe reaction was filtered
  4. customto remove the sodium sulfate
  5. customthe solvent was removed in vacuo
  6. dissolutionThe residue was dissolved in 25 mL of dichloromethane
  7. extractionextracted with 2×10 mL of water
  8. additionThe aqueous phase was diluted with 50 mL ethanol
  9. concentrationconcentrated in vacuo
  10. customleaving an off-white solid
  11. filtrationfiltered through a 0.2 □m polypropylene membrane

Sources & evidence

ORD record
ord-0b36c9c2bcb5453cbbb8549ee27ee9d8
Source dataset
uspto-grants-2010_03
Patent number
US07683168B2

Reaction notes

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