Sodium Hydroxide → HCID 11163902, compound

HRID 1064761Notes

Reaction equation

HRID 1064761 reaction equation
[CH3:1][C@@H:2]1[CH2:6][CH2:5][CH2:4][N:3]1[CH2:7][CH2:8][C:9]1[O:10][C:11]2[CH:17]=[CH:16][C:15]([C:18]3[CH:19]=[C:20]([CH:26]=[CH:27][CH:28]=3)[C:21]([O:23]CC)=[O:22])=[CH:14][C:12]=2[CH:13]=1.[OH-].[Na+]>C(O)C>[CH3:1][C@@H:2]1[CH2:6][CH2:5][CH2:4][N:3]1[CH2:7][CH2:8][C:9]1[O:10][C:11]2[CH:17]=[CH:16][C:15]([C:18]3[CH:19]=[C:20]([CH:26]=[CH:27][CH:28]=3)[C:21]([OH:23])=[O:22])=[CH:14][C:12]=2[CH:13]=1

Participants

4

Reactant 2

HCID 14798Sodium HydroxideHCID 67533825HCID 67533825, compound

Product 1

HCID 11163902HCID 11163902, compound

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Conditions

Temperature
55 °C

Procedure

The product from Example 143C (755 mg, 2 mmol) was dissolved into ethanol (20 mL) and treated with 2 M aqueous NaOH (2 mL). The mixture was heated at 55° C. for 40 minutes, cooled to room temperature, concentrated, and partitioned between isopropanol and a mixture of 1 M aqueous potassium dihydrogen phosphate and brine. The aqueous phase was separated and extracted with isopropanol, and the combined organic phases were washed with a mixture of pH 6 potassium phosphate buffer and brine. The aqueous phase was separated and extracted with isopropanol, and the combined organic phases were washed with brine. Again, the aqueous phase was separated and extracted with isopropanol, and the combined organic phases were diluted with EtOAc, and filtered. The filtrate was dried (Na2SO4) and concentrated. The residue was chromatographed on silica with 50% EtOAc/CH2Cl2, followed by 10% MeOH/45% EtOAc/CH2Cl2, followed by 30% MeOH/CH2Cl2. The appropriate fractions were concentrated and the residue dissolved into EtOAc/CH2Cl2, and the solids which precipitated were washed with additional EtOAc/CH2Cl2 to provide the title compound as a white powder. MS (ESI APCI) m/z 350 (M+H)+; 1HNMR (300 MHz, CD3OD) δ 1.39 (s, 3 H), 1.58-1.76 (m, 1 H), 1.91-2.10 (m, 2 H), 2.16-2.31 (m, 1 H), 2.89-3.04 (m, 1 H), 3.08-3.3 (m, 4 H), 3.50-3.71 (m, 2 H), 6.70 (s, 1 H), 7.39-7.59 (m, 3 H), 7.69 (d, 1 H), 7.79 (s, 1 H), 7.92 (d, 1 H), 8.23 (s, 1 H).]

Workup

  1. temperaturecooled to room temperature
  2. concentrationconcentrated
  3. custompartitioned between isopropanol
  4. additiona mixture of 1 M aqueous potassium dihydrogen phosphate and brine
  5. customThe aqueous phase was separated
  6. extractionextracted with isopropanol
  7. washthe combined organic phases were washed with a mixture of pH 6 potassium phosphate buffer and brine
  8. customThe aqueous phase was separated
  9. extractionextracted with isopropanol
  10. washthe combined organic phases were washed with brine
  11. customAgain, the aqueous phase was separated
  12. extractionextracted with isopropanol
  13. additionthe combined organic phases were diluted with EtOAc
  14. filtrationfiltered
  15. dry with materialThe filtrate was dried (Na2SO4)
  16. concentrationconcentrated
  17. customThe residue was chromatographed on silica with 50% EtOAc/CH2Cl2
  18. concentrationThe appropriate fractions were concentrated
  19. dissolutionthe residue dissolved into EtOAc/CH2Cl2
  20. customthe solids which precipitated
  21. washwere washed with additional EtOAc/CH2Cl2

Sources & evidence

ORD record
ord-d34cc20f0caa48ccaa3a3ab09dc06c82
Source dataset
uspto-grants-2005_11
Patent number
US06969730B2

Reaction notes

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